JPS60169438A - Synthesis of p-hydroxybenzoic acid - Google Patents

Abstract

PURPOSE:To obtain the titled compound useful as a raw material of agricultural chemicals, etc., in high yield, without necessitating particular expensive reaction apparatuses, etc., by using a specific solid catalyst in the reaction of a phenol with carbon tetrahalide in the presence of an alkali. CONSTITUTION:The objective compound is produced by reacting a phenol with carbon tetrahalide in the presence of sodium hydroxide or potassium hydroxide using a solid catalyst obtained by crosslinking the hydroxyl group of cyclodextrin with hydroxypropyl group. The above solid used as the catalyst can be prepared e.g. by reacting cyclodextrin with epichlorohydrin or epibromohydrin in an alkaline aqueous solution. The cyclodextrin is preferably beta-cyclodextrin, and the molar ratio of the cyclodextrin in the reaction mixture to the phenol is preferably >=0.01.

Description

[Detailed description of the invention] The present invention relates to a method for synthesizing rose hydroxybenzoic acids.

Rose hydroxybenzoic acids are heat-resistant polymers.

Its importance as a raw material for agricultural chemicals and medicines has increased recently.

So far, phenol or cresol has been treated with potassium hydroxide and potassium carbonate, and then under pressure, carbon dioxide and t
The method for synthesizing parahydroxybenzoic acids by heating to J-, l-1 is described by Kolbe-8chmitt
It was known as a reaction. However, this reaction requires expensive reactor equipment due to the high pressure reaction and the inability to achieve the highly anhydrous conditions essential for the reaction.
It has disadvantages such as requiring a large amount of thermal energy to evaporate water.

A method for synthesizing parahydroxybenzoic acid by reacting phenol and carbon tetrachloride in the presence of an alkali was also known. However, the selectivity for the production of parahydroxybenzoic acid in this reaction is about 50%, and a large amount of salicylic acid is produced as a by-product. Therefore, obtaining bara hydroxybenzoic acid by this method required a large amount of raw materials and nine separation operations.

In the present invention, when reacting phenols with carbon tetrahalide in the presence of an alkali, by adding a solid in which the hydroxyl groups of cyclodextrin are cross-linked with hydroxypropyl groups, the target product, hydroxybenzoic acids, can be obtained. This product significantly improves the efficiency and selectivity, saves raw materials, and simplifies separation operations.

Namely, the present inventors used phenols and sodium hydroxide in an aqueous solution of potassium hydroxide.

By adding a solid in which the hydroxyl groups of cyclodextrin are cross-linked with hydroxypropyl groups, and then adding carbon tetrahalide, hydroxybenzoic acids can be produced in high yield.
We succeeded in synthesizing it with high selectivity. Both the yield and selectivity of rose hydroxybenzoic acids, which are the target products of the present invention, are approximately 100%.

The phenol described in the specification. For example,

Phenol, 2-position substituted phenol, 3-position substituted phenol, 2-position, 3-position disubstituted phenol, 3-position.

These include 5-position disubstituted phenol, and 2- and 5-position disubstituted phenol. Here, the substituent of phenol is
Examples include saturated and unsaturated hydrocarbon groups having 1 to 6 carbon atoms, aryl groups, cyano groups, and halogens.

Describe it in the specification. What is a solid made by crosslinking the hydroxyl groups of cyclodextrin with hydroxypropyl groups?

For example, it is a solid obtained by reacting cyclodextrin with shrimp chlorohydrin or shrimp bromohydrin in an alkaline aqueous solution.

As the cyclodextrin, both α-7 clodextrin and β-cyclodextrin can be used, but β-cyclodextrin is more effective. In order to obtain hydroxybenzoic acids with a selectivity close to 100%, the amount of the solid in which the hydroxyl groups of cyclodextrin are cross-linked with hydroxypropyl groups is as follows:
Although it is desirable that the molar ratio of the cyclodextrin contained to the phenol is 0.01 or more, an improvement in the selectivity in the production of parahydroxybenzoic acids can be achieved even if the amount is less than this.

This reaction proceeds rapidly in the presence of a copper catalyst.

Here, the copper catalyst is, for example, copper powder or copper sulfate (■).

Copper halides (formerly) and copper oxides (formerly, etc.) However, it is possible to carry out one reaction without using a copper catalyst.

In the present invention, the solid in which the hydroxyl groups of cyclodextrin are crosslinked with hydroxypropyl groups does not change during the reaction and is easily separated and recovered after 8 reactions by a method such as filtration. Separate and collect solids.

No deterioration in the two-selectivity was observed when the catalyst was used again as a catalyst.

Next, the present invention will be specifically explained with reference to Examples, but the present invention is not limited thereto.

Example I Journal of Macromolecular
5science, - Chernistry magazine, Volume A, No. 5, published in 1973.

A solid in which the hydroxyl groups of β-cyclodextrin were crosslinked with hydroxypropyl groups was prepared by the method described on page 1149.

50g of β-cyclodextrin (manufactured by Hanui Chemical Co., Ltd., special grade reagent) was added to 50% sodium hydroxide aqueous solution 8Q.
++tl, and 50 mg of sodium borohydride (manufactured by Yoneyama Pharmaceutical Co., Ltd., special grade reagent) was added. While stirring this solution using a magnetic stirrer, 34 m
1 was added dropwise, and the mixture was reacted at 50° C. for 40 minutes. After washing the generated solid three times with acetone and thoroughly with water,
After vacuum drying at ℃ for 12 hours, a solid consisting of white particles each having a particle size of about 1 to 3 plates was obtained. This is the catalyst.

Add 1.5 g of this catalyst and 1.5 g of phenol (manufactured by Koso Chemical Co., Ltd., - grade reagent) to 20 ml of 20% aqueous sodium hydroxide solution, and add 3 ml of carbon tetrachloride (
(manufactured by Tokyo Kasei Kogyo Co., Ltd., − grade reagent) and 0.1 g of copper powder (manufactured by Yoneyama Pharmaceutical Co., Ltd.).

- grade reagent) was added. The reaction solution was stirred using a magnetic stirrer and heated to 80°C while being refluxed using a water reflux device.
The mixture was allowed to react for 15 hours. After reaction.

The catalyst was removed by decantation. The resulting reaction solution was made acidic with hydrochloric acid, extracted three times with 50 TLl of ether, and the ether layer was washed with water and then dried.

2.1 g of product was obtained. The product was analyzed by liquid chromatography (Toyo Soda Co., Ltd. column, LS41.

When analyzed with K, MeOH-100, 30 cm, 25°C, water-ethanol 6:4 mixed solvent), the product was 2.
It was a mixture of 0g of rose hydroxybenzoic acid and 0.1g of phenol, and no salicylic acid was observed. That is, the yield of parahydroxybenzoic acid was 91 mol% and the selectivity was 100%.

Next, the catalyst separated after the above reaction and 1.5 g of phenol were added to 2011 liters of a 20% aqueous sodium hydroxide solution, and 3 ml of carbon tetrachloride and 0.1 g of copper powder were added thereto. The reaction solution was stirred using a magnetic stirrer and reacted at 80° C. for 15 hours while refluxing using a water flow device. After reaction.

The catalyst was removed by decantation. The resulting reaction solution was made acidic with hydrochloric acid, extracted three times with 5 ornl of ether, and the ether layer was washed with water and dried.

2.2 g of product was obtained. Analysis of the product by liquid chromatography revealed that the product was a mixture of 2.1 g of parahydroxybenzoic acid and 0.1 g of phenol, and no salicylic acid was found to be present.

That is, the yield of rose hydroxybenzoic acid is 95 mol%
The 1 selectivity was 10()%.

The catalyst was similarly used 5 times thereafter, but no deterioration was observed in the activity and selectivity of the catalyst.

Example 2 The same reagents and catalysts as in Example 1 were used, except that 0-cresol (manufactured by Tokyo Kasei Co., Ltd., special grade reagent) was used instead of the phenol described in Example 1.

In Example 1, 1.5 g of the catalyst prepared from β-cyclodextrin and shrimp chlorohydrin and 1.5 g of O-cresol were added to 20 ml of 20% aqueous sodium hydroxide solution, and 3 ml of carbon tetrachloride was added thereto. and 0.1 g of copper powder were added. The reaction solution was stirred using a magnetic stirrer and allowed to react at 80° C. for 15 hours while flowing back using a water streamer. After reaction.

The catalyst was removed by decantation. The resulting reaction solution was made acidic with hydrochloric acid, extracted three times with 501 nl of ether, and the ether layer was washed with water and then dried.

1.9. Product F was obtained. The product was subjected to liquid chromatography (column L8410 manufactured by Toyo Soda Co., Ltd.).
When analyzed using MeOH-100, 30Cm, 25°C, water-ethanol 6:4 mixed solvent, the product was 1.8g of 3-methyl-4-hydroxybenzoic acid and 0.1g of O-
It was a mixture of cresols.

That is, the yield of 3-methyl-4-hydroxybenzoic acid was 85 mol% and the 1 selectivity was 100%.

Example 3 The same reagents and catalysts as in Example 1 were used, except that m-cresol (manufactured by Tokyo Kasei Co., Ltd., special grade reagent) was used instead of the phenol described in Example 1.

In Example 1, the catalyst prepared from β-cyclodextrin and shrimp chlorohydrin 1.5,! il and 1.59 m
-Cresol was added to 20 m of 20% aqueous sodium hydroxide solution, to which were added 3 ral of carbon tetrachloride and 0.1 g of copper powder. The reaction solution was stirred using a magnetic stirrer and heated to 80°C for 15 minutes while being refluxed using a water streamer.
I let it react over time. After reaction.

The catalyst was removed by decantation. The resulting reaction solution was made acidic with hydrochloric acid, extracted three times with 5 Qml of ether, and the ether layer was washed with water and dried.

2.1 g of product was obtained. The product was subjected to liquid chromatography (Toyo Soda Co., Ltd. column, LS41oK, M
eOH-100, 30℃m, 25℃, water-ethanol 6
:4 mixed solvent), the product was 2.0g of 2
-Methyl = a mixture of 4-hydroxybenzoic acid and 0.1 g m-cresol.

That is, the yield of 2-methyl-4-hydroxybenzoic acid was 95 mol% and the 8 selectivity was 100%.

Example 4 The same reagents as in Example 1 were used, except that copper sulfate (manufactured by Yotsuhata Chemical Industry Co., Ltd., − grade reagent, pentahydrate salt) was used instead of the copper powder described in Example 1.

50 g of β-cyclodextrin was dissolved in 80 TL of 50% aqueous sodium hydroxide solution, and 50 μ of sodium borohydride was added. While stirring this solution using a magnetic stirrer, 68 ml of epichlorohydrin was added dropwise and reacted at 50° C. for 40 minutes. After washing the generated solid three times with acetone and thoroughly with water, it was heated at 60°C for 12
h Vacuum dry.

A solid consisting of white particles with a particle size of about 1 to 3 mm was obtained. This is the catalyst.

Add 1.5 g of this catalyst and 1.5 I of phenol to 20 ml of 20% phenol solution, and add to a 3 m
1 of carbon tetrachloride and 0.1 g of copper powder were added.

The reaction solution was stirred using a magnetic stirrer and reacted at 80° C. for 15 hours while flowing 8 times using a water jet drifter. After the reaction, the catalyst was removed by decantation. The resulting reaction solution was made acidic with hydrochloric acid, extracted three times with 501 nl of ether, and the ether layer was washed with water and dried.
．． 9.9 of the product was obtained.

When the product was analyzed by liquid chromatography (Toyo Soda Co., Ltd. %3Qcm, 25°C, water-ethanol 6:4 mixed solvent), the product was a mixture of 1.8g of rose hydroxybenzoic acid and 0.1g of phenol. there were. That is, the yield of parahydroxybenzoic acid was 82 mol% and the 2 selectivity was 100%.

Patent applicant Hidefumi Hirai

Claims (1)

[Claims] When reacting phenols with carbon tetrahalide in the presence of sodium hydroxide or potassium hydroxide, a solid in which the hydroxyl groups of cyclodextrin are cross-linked with hydroxypropyl groups is used as a catalyst to react with parahydroxybenzoic acids. A highly selective manufacturing method.