JPH027310B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing an indole compound from an indoline compound. Conventionally, oxidation from indoline nucleus to indole nucleus has been performed using manganese dioxide, cupric chloride-pyridine,
There are methods using chloranil, palladium black, etc. However, since the indole nucleus is susceptible to oxidation, there is a problem in that the reaction conditions must be carefully considered, and there is also a risk that the functional groups on the nucleus will be oxidized. Moreover, in the case of mass production, disposal of the used inorganic oxidizing agent also becomes a serious problem. As a result of various studies aimed at solving the drawbacks of these conventional techniques, the present inventors succeeded in obtaining an indole compound by dehydrogenating an indoline compound under extremely mild conditions, and completed the present invention. In the present invention, an indoline compound and a sulfide are reacted in the presence of an organic base at -40 to -80°C by adding tertiary butyl hypochloride, and then an organic base is added to the reaction. This is a method for producing indole compounds. In the present invention, the indoline compound means indoline or "an indoline derivative in which no substituent is present on the nitrogen atom of the indoline nucleus." 1 of the indoline nucleus as long as it does not interfere with the reaction between the nitrogen atom of the indoline nucleus and the sulfide.
Any substituent may be present other than the position. The indole compound means a compound corresponding to each of the above-mentioned indoline compounds. Sulfide means a sulfide having a methyl group or methylene group next to a sulfur atom, and dimethyl sulfide is preferred. Organic base means basic organic substances such as organic amines and sodium alcoholates. This reaction can be carried out at -40 to -80°C, and -
Cooling to around 60℃ gives good results. The present invention is carried out as follows. That is, a solution in which an indoline compound, an approximately equimolar amount of an organic base, and a small excess of sulfide are dissolved in an aprotic organic solvent (e.g., methylene chloride, acetonitrile, dimethoxyethane, etc.) is heated at -40 to -80°C. tertiary butyl hypochloride in an approximately equimolar amount is added dropwise thereto, and the mixture is reacted with stirring for 1 to 2 hours while maintaining the temperature to produce an azasulfonium salt.
After adding about 5 times the mole of an alcoholic solution of an organic base to this, cooling is stopped and the temperature of the reaction system is returned to room temperature. The time required for this is approximately 2 hours. This reaction solution can be post-treated by a conventional method to obtain an indole compound in good yield. In the production method of the present invention, the reaction conditions are extremely mild, so even if other functional groups exist in the raw material compounds, they will not be affected, and even if the compound is optically active, its activity will not be impaired. There isn't.
In addition, the reaction operation is extremely simple as it only requires mixing under cooling. Next, the present invention will be specifically explained with reference to Examples. Example 1 Indoline (3 mmol), dimethyl sulfide (4.5 mmol) and triethylamine (3 mmol)
was dissolved in methylene chloride (10 ml) and heated at -65°C.
A solution of butylhypochloride (3.9 mmol) in methylene chloride (10 ml) was added dropwise thereto. This reaction solution was kept as it was for 2 hours, and then methanol (5
ml) and sodium metal (15 mmol) was added over a period of 10 minutes, cooling was stopped, and stirring was continued to allow the mixture to return to room temperature. This took two hours. Add water (20
ml), the aqueous layer was extracted 30 times with methylene chloride (2 ml), the extracts were combined, and saturated brine (20 ml) was added.
and dried with Glauber's salt. This dry extract was distilled off under reduced pressure, and the resulting residue was purified by silica gel column chromatography (developing solvent benzene-hexane 1:1) and recrystallized from water to obtain indole in a yield of 82%. . mP52-53°C Example 2 By treating the corresponding raw material compounds in the same manner as in Example 1, the compounds shown in the following table could be obtained. 【table】

Claims (1)

[Claims] 1. An indole compound characterized by reacting an indoline compound and a sulfide with tertiary butyl hypochloride at -40 to -80°C in the presence of an organic base, and then adding an organic base thereto. Method of manufacturing compounds.