JPH0212220B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for the synthesis of indole-3-aldehydes.

Indole-3-aldehyde is used as an antibacterial agent and as an intermediate for various pharmaceuticals and agricultural chemicals.
Its importance has been increasing recently.

Already, indole-
Methods for synthesizing 3-aldehydes were known.
However, as seen in Comparative Example 1 below, in this reaction, a large amount of 3-chloroquinoline produced by ring expansion of indole is produced as a by-product, resulting in a high yield and selectivity of the target indole-3-aldehyde. is low. Therefore, in order to obtain indole-3-aldehyde by this method, a large amount of raw materials and separation operations were required.

By adding cyclodextrin, which is a cyclic oligosaccharide, to the above reaction system, the present invention significantly improves the yield and selectivity of the target product, indole-3-aldehyde, and saves raw materials and separation operations. This has achieved simplification.

That is, the present inventors synthesized indole-3-aldehyde with high yield and high selectivity by adding cyclodextrin to an aqueous solution of indole and sodium hydroxide or potassium hydroxide, dissolving it, and then adding chloroform. succeeded in doing so. Both the yield and selectivity of indole-3-aldehyde, which is the target product of the present invention, are approximately 100%.

As the cyclodextrin, both α-cyclodextrin and β-cyclodextrin can be used, but β-cyclodextrin is more effective. In order to obtain indole-3-aldehyde with a selectivity close to 100%, the amount of cyclodextrin added is preferably 0.5 or more in terms of molar ratio to the chloroform present in the reaction system; Even with the amount of dextrin used, improved selectivity in the production of indole-3-aldehyde is achieved.

The concentration of the aqueous solution of sodium hydroxide or potassium hydroxide in the present invention is 0.1 to 50% by weight, preferably 5 to 20%. In addition, the reaction temperature is 30~
The temperature is 120°C, preferably 50-80°C.

Cyclodextrin does not change during the reaction and can be reused as is after the reaction. After the reaction, when the reaction system is made acidic, cyclodextrin precipitates due to decreased solubility. More than 80% of the cyclodextrin can be recovered using this simple method, and the recovered cyclodextrin can be completely reused.

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

Example 1 1.2 g (10.3 mmol) of indole (manufactured by Tokyo Chemical Industry Co., Ltd., special grade reagent) and 8.0 g (7.0 mmol) of β-cyclodextrin (manufactured by Hanui Chemical Co., Ltd., special grade reagent) were added to 50 ml of 20% Dissolved in aqueous sodium hydroxide solution. While 3 ml (37.4 mmol) of chloroform (manufactured by Tokyo Chemical Industry Co., Ltd., special grade reagent) was added dropwise thereto, the reaction solution was stirred using a magnetic stirrer and allowed to react at 60°C for 10 hours. After the reaction, the 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 dried to obtain 1.41 g of product.
Manufactured by Okura Rikagaku Kenkyusho, 701 type gas chromatograph (filling material Manufactured by Gas Chrom Industrial Co., Ltd., Tenax
As a result of analysis using Gc; column length, 2 m; column temperature 300°C, carrier gas, helium), all the products were indole-3-aldehyde, and 3-chloroquinoline was not detected. That is, the yield of the target product was 95 mol%, and the selectivity was 100%.

Comparative Example 1 All reagents were the same as those described in Example 1. 1.2 g (10.3 mmol) of indole was dissolved in 50 ml of 20% aqueous sodium hydroxide solution, and 3 ml (37.4 mmol) of chloroform was added dropwise thereto, while the reaction solution was stirred using a magnetic stirrer. The reaction was carried out at ℃ for 10 hours. After the reaction, acidify the reaction solution with hydrochloric acid and add 50ml.
The extract was extracted three times with ether, and the ether layer was washed with water and dried to obtain 0.34 g of product. As a result of analysis using a model 701 gas chromatograph manufactured by Okura Rikagaku Kenkyusho, the product was a mixture of 0.16 g of indole-3-aldehyde and 0.18 g of 3-chloroquinoline. That is, the yield of the target product was 11 mol%, and the selectivity was 50%.

Claims (1)

[Claims] 1. A method for highly selectively producing indole-3-aldehyde by using cyclodextrin as a catalyst in reacting indole with chloroform in the presence of sodium hydroxide or potassium hydroxide.