JPS60215645A - Synthetic method of p-hydroxybenzaldehyde - Google Patents

Abstract

PURPOSE:To obtain the titled compound in high yield and selectivity with easy separating operation and saved raw material, by reacting a phenol with chloroform in the presence of an alkali and a specific solid catalyst. CONSTITUTION:A phenol is reacted with chloroform in the presence of a solid obtained by crosslinking hydroxyl groups in cyclodextrin with hydroxypropyl groups as a catalyst and sodium or potassium hydroxide to give the aimed compound. The phenol includes phenol, 2-substituted phenol, etc. The solid obtained by crosslinking the hydroxyl groups in the cyclodextrin with hydroxypropyl groups is e.g. a solid obtained by reacting the cyclodextrin with epichlorohydrin or epibromohydrin in an aqueous solution of an alkali. The amount of the catalyst to be added is preferably >=0.5 molar ratio of the cyclodextrin to the phenol.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for synthesizing rosehydroquine benzaldehydes.

Parahydroxybenzaldehydes are used as anticancer agents or as intermediates for pharmaceuticals, agricultural chemicals, dyes, etc.
Its importance has been increasing recently.

Conventionally, a method for synthesizing parahydroxybenzaldehyde by reacting phenol and chloroform in the presence of an alkali has been known.

However, the selectivity for producing parahydroxybenzaldehyde in this reaction is about 30%.

A large amount of salicylaldehyde is produced as a by-product. Therefore.

Obtaining parahydroxybenzaldehyde by this method required a large amount of raw materials and nine separation operations.

In the present invention, when reacting phenols and chloroform in the presence of an alkali, by adding a solid in which the hydroxyl groups of cyclodextrin are crosslinked with hydroxypropyl groups, the yield and selection of parahydroxybenzaldehydes, which are the target products, are improved. This has significantly improved performance, saved raw materials, and simplified separation operations.

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

By adding a solid in which the hydroxyl groups of cyclodextrin are cross-linked with hydroxypropyl groups, and then adding chloroform, we succeeded in synthesizing para-hydroxybenzaldehydes in high yield and with high selectivity. Both the yield and selectivity of rosehydroquine benzaldehyde, which is the target product of the present invention, are approximately 100%.

The phenols described in the specification include, for example, phenol, 2-substituted phenol, 3-substituted phenol, 3-substituted phenol,
5-position disubstituted phenol, and.

These include disubstituted phenols at the 2- and 5-positions. Here.

Substituents for phenol include, for example, saturated and unsaturated hydrocarbon groups having 1 to 6 carbon atoms, aryl groups, hydroxyl groups, carboxyl groups, sulfonic acid groups, and halogens.

Describe it in the specification. What is a solid whose hydroxyl groups are crosslinked 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-cyclodextrin and β-cyclodextrin can be used, but β-cyclodextrin is more effective. As a solid additive in which the hydroxyl groups of cyclotegistone are crosslinked with hydroxypropyl groups, in order to obtain parahydroxybenzaldehydes with a selectivity close to 100%.

It is desirable that the molar ratio of the cyclodextrin contained to the phenol is 0.5 or more.

Even if the amount is less than this, selection and improvement in the production of parahydroxybenzaldehydes can be achieved.

In the present invention, the solid in which the hydroxyl groups of cyclodextrin are cross-linked with hydroxypropyl groups is a two-particulate solid that does not dissolve in the two reaction systems, and does not chemically change during the reaction. Therefore, one reaction wave can be easily separated and recovered from one reaction system by methods such as centrifugal shear separation or filtration. Even when the separated and recovered solid was used again as a catalyst, no deterioration in the two-selectivity was observed.

sifurobukis (non-crosslinked with hydroxypropyl groups)
When +7ton is used as a catalyst, the catalyst is smeltable. Therefore, in order to recover cyclodextrin after one reaction, it is necessary to add acid to the reaction system to make it acidic and reduce the solubility of cyclodextrin.
This results in a loss of 20%. From this, it is clear that the method of the present invention using a catalyst in which the hydroxyl groups of cyclodextrin are crosslinked with hydroxypropyl groups is superior in terms of ease of catalyst separation and resource saving.

The present invention can also be carried out by using a fixed bed of a solid obtained by crosslinking the hydroxyl groups of cyclodextrin with hydroxypropyl groups, and passing an alkaline aqueous solution of phenol and chloroform through this fixed bed or bringing it into contact with the fixed bed. EXAMPLES Next, the present invention will be described in detail with reference to two examples, but the present invention is not limited thereto.

[Example 1] Journal of Macromolecular
A solid in which the hydroxyl group of β-7 clodextrin was crosslinked with a hydroxypropyl group was prepared by the method described in 5science, -Che-mistry magazine, Vol. A, No. 5, 1973, page 1149.

50.9 β-cyclodextrin (manufactured by Hanui Chemical Co., Ltd., special grade reagent) in a 50% sodium hydroxide aqueous solution 8
0ml dissolved in 50ml of sodium borohydride (
Yoneyama Pharmaceutical Co., Ltd., special grade reagent) was added. While stirring this solution using a magnetic stirrer, add 34 ml of shrimp chlorohydrin (manufactured by Tokyo Kasei Co., Ltd., special grade reagent).
was added dropwise and reacted at 50'C for 40 minutes. The resulting solid was washed three times with acetone. This is the catalyst.

This catalyst 4.50g and 0.50! ! phenol (manufactured by Koso Chemical Co., Ltd.).

- grade reagent) was added to 50 ml of 20% aqueous sodium hydroxide solution, and the two reaction solutions were heated to 60° C. while stirring using a magnetic stirrer. The reaction was allowed to proceed for 12 hours while dropping 3 ml of chloroform (manufactured by Tokyo Chemical Industry Co., Ltd., special grade reagent). After the reaction, the catalyst was removed with Decanchi/Con. After making the obtained reaction solution acidic with hydrochloric acid, 5or
The extract was extracted three times with nll of ether, and the ether layer was washed with water and dried to obtain 0.58 g of product. The product was analyzed using a gas chromatograph (Tenax GC column, 2 m, 3
Analysis at 0.000C revealed that the product was a mixture of 056I 4-hydroxybenzaldehyde and 0.02.9% phenol.

2-Hydroxybenzaldehyde was not detected.

That is, the yield of 4-hydroxybenzaldehyde is 8
The Ashi 22 selectivity was 100% with 4 molti.

Next, the catalyst separated after the above reaction and 0.50.9 phenol were added to 50 ml of 20% sodium hydroxide aqueous solution, and the reaction solution was heated to 60°C while stirring using a magnetic stirrer. . The reaction was continued for 12 hours while adding 3 ml of chloroform dropwise. After the reaction, the catalyst was removed by decantation. The resulting reaction solution was made acidic with hydrochloric acid, extracted three times with 50 ml of ether, and the ether layer was washed with water and then dried.

065 g of product' were obtained. When the product was analyzed by gas chromatography, the product was a mixture of 062 g of 4-hydroxybenzaldehyde and 0.03 g of phenol, and no 2-hydroxybenzaldehyde was detected. That is, the yield of 4-hydroxybenzaldehyde was 94 moles.

The selectivity was 100.

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

In Example 1, 450 g of the catalyst prepared from β-7 clodextrin and shrimp chlorohydrin and 0.50.9 0-cresol were added to 501 nl of a 20% aqueous sodium hydroxide solution, and the two reaction solutions were mixed using a magnetic stirrer. While stirring, the mixture was heated to 60°C. The reaction was allowed to proceed for 12 hours while dropping 3 ml of chloroform (manufactured by Tokyo Chemical Industry Co., Ltd., special grade reagent). After the reaction, the catalyst was removed by decantation. After making the obtained reaction solution acidic with hydrochloric acid, 50+
++A' was extracted three times with ether, and the ether layer was washed with water and dried to obtain 0.65 g of product. When the product was analyzed by gas chromatography, the product was 0.6
It was a mixture of 1 g of 4-hydroxy-3-methylbenzaldehyde and 0.04 g of 0-cresol. That is, the yield of 4-hydroxy-3-methylbenzaldehyde was 82 mol, and the 2 selectivity was 100%.

Patent applicant Hidefumi Hirai

Claims (1)

[Claims] When reacting phenols with chloroform 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, resulting in highly selective reaction to parahydroxybenzaldehydes. How to manufacture.