CN110526852B

CN110526852B - Preparation method of indole

Info

Publication number: CN110526852B
Application number: CN201910880937.5A
Authority: CN
Inventors: 黄崇琛
Original assignee: Hubei Sibo Chem Co ltd
Current assignee: Hubei Sibo Chem Co ltd
Priority date: 2019-09-18
Filing date: 2019-09-18
Publication date: 2020-10-09
Anticipated expiration: 2039-09-18
Also published as: CN110526852A

Abstract

The invention discloses a preparation method of indole, which is to synthesize the indole in one step by taking o-aminophenylethanol as a raw material through catalytic oxidation condensation, and specifically comprises the following steps: dissolving o-aminophenylethanol in an organic solvent, adding a catalyst, controlling the reaction temperature to be 20-50 ℃, and introducing air or oxygen until the reaction is complete; the dosage of the catalyst is 0.02-0.08 g/g of raw materials, and the catalyst comprises at least one of cobalt acetate and manganese acetate and N-hydroxyphthalimide; the invention reduces the cost by low-temperature air oxidation condensation, the required reaction condition is mild, the potential safety hazard is eliminated, and the final indole yield reaches more than 90 percent.

Description

Preparation method of indole

Technical Field

The invention relates to the technical field of chemical synthesis, in particular to a preparation method of indole.

Background

Indole is white crystal, is metabolite of animal tissue, and can be used in a series of medicinal products, bioactive substances, dyes, perfumes, etc. Indole is an important fine chemical intermediate, and is an important raw material for producing spices, printing and dyeing, and medicines for preventing and treating cardiovascular diseases, neurological diseases and tumors and enhancing immunity. One of the most important uses is the synthesis of tryptophan as an intermediate, which can be used as a highly effective feed additive. The indole originally was obtained mainly from coal tar and contained about 2-3% in the 220 ℃ and 270 ℃ fractions. But is not easy to separate, has large energy consumption and complex refining process. Later, fermentation methods as well as synthetic methods were developed. The synthesis of indole in industry has several routes as follows:

route one: purifying the coal tar to obtain the product;

and a second route: obtained by condensing o-toluidine and formic acid at high temperature;

and a third route: is obtained by high-temperature condensation of aniline and ethylene glycol;

and a fourth route: condensing o-nitrotoluene and formaldehyde to obtain o-nitroanisole, hydrogenating to obtain o-aminophenylethanol, and dehydrocyclizing with Raney nickel to obtain indole;

in the synthesis process, the first route is restricted by the source of raw materials; in the second route, a large amount of alkaline residues and acid residues exist, the temperature is 300 ℃, and the conditions are harsh; the third route mainly has the problems of catalyst development and higher reaction temperature; the source of the raw materials in the fourth route is wide, the cost is low, the production is flexible, the conditions are mild, raney nickel which is easy to catch fire is adopted as a catalyst in the o-aminophenylethanol dehydrogenation process, hydrogen is continuously generated in the process, the hydrogen needs to be blown away from a reaction system in time, the potential safety hazard is great, and the product yield is only about 80%.

How to develop a preparation method of indole with high safety, mild required reaction conditions and high product yield is a technical problem to be solved urgently.

Disclosure of Invention

The invention aims to overcome the defects of the prior art and provides a preparation method of indole, which reduces the cost by low-temperature air oxidation condensation, relieves the required reaction conditions, eliminates the potential safety hazard and finally obtains the indole with the yield of more than 90 percent.

The invention is realized by the following steps:

the invention aims to provide a preparation method of indole, which is to synthesize the indole in one step by taking o-aminophenylethanol as a raw material through catalytic oxidation condensation, and specifically comprises the following steps:

dissolving o-aminophenylethanol in an organic solvent, adding a catalyst, controlling the reaction temperature to be 20-50 ℃, and introducing air or oxygen until the reaction is complete;

the dosage of the catalyst is 0.02-0.08 g/g of raw materials, and the catalyst comprises at least one of cobalt acetate and manganese acetate and N-hydroxyphthalimide.

Preferably, the solvent is chloroform; the ratio of the volume of the added solvent to the molar weight of the o-aminophenylethanol is 40-60: 0.1 mL/mol.

Preferably, the catalyst is N-hydroxyphthalimide and cobalt acetate; the mass ratio of the N-hydroxyphthalimide to the cobalt acetate is 0.15-0.4: 0.1 to 0.7.

Preferably, the reaction temperature is 30-40 ℃.

Preferably, air is introduced as the oxidizing agent.

Preferably, after the reaction is completed, the reaction liquid is sent to reduced pressure distillation for purification.

Compared with the prior art, the invention has the following advantages and effects:

1. the invention provides a preparation method of indole, which takes o-aminophenylethanol as a raw material, N-hydroxyphthalimide and cobalt acetate (and/or manganese acetate) as catalysts, air or oxygen is introduced as an oxidant, indole is synthesized in one step by catalytic oxidation condensation (the reaction formula is shown in figure 2), and finally the yield of the obtained indole reaches over 90 percent.

2. The preparation method of indole provided by the invention develops a new synthesis process, reduces the cost through low-temperature air oxidation condensation, and eliminates the potential safety hazard due to mild reaction conditions.

Drawings

FIG. 1 is a chromatogram of indole prepared in example 1 of the present invention;

FIG. 2 is a reaction scheme of the process for preparing indole according to the present invention.

Detailed Description

Example 1

At room temperature, 13.7 g of o-aminophenylethanol (0.1 mol) is dissolved in 40 ml of trichloromethane in a 500 ml three-necked bottle, 0.4 g of N-hydroxyphthalimide and 0.7 g of cobalt acetate are added, the temperature is kept at 30 ℃ in a water bath, 50 ml/min of air is introduced, magnetic stirring is started, sampling detection is carried out to monitor the complete conversion of the o-aminophenylethanol, and air blowing is stopped.

The reaction solution is subjected to reduced pressure distillation, so that 11.07 g (0.0946 mol) of indole is obtained, the molar yield is 94.6%, the purity is 99.9%, a flat head peak in 2.0 minutes in a chromatogram 1 is ethanol which is an analysis solvent of a dissolved product, an indole peak is 15.88 minutes, the retention time of the peak is 15.88min, and the peak area is 99.99%.

Example 2

At room temperature, 13.7 g of o-aminophenylethanol (0.1 mol) is dissolved in 60 ml of trichloromethane in a 500 ml three-necked bottle, 0.4 g of N-hydroxyphthalimide and 0.7 g of manganese acetate are added, the temperature is kept at 40 ℃ in a water bath, 50 ml/min of air is introduced, magnetic stirring is started, sampling detection is carried out to monitor the complete conversion of the o-aminophenylethanol, and the introduction of the air is stopped.

The reaction mixture was subjected to distillation under reduced pressure to give indole in an amount of 10.58 g (0.0904 mol), in a molar yield of 90.4% and a purity of 99.1%.

Example 3

At room temperature, 13.7 g of o-aminophenylethanol (0.1 mol) is dissolved in 50 ml of trichloromethane in a 500 ml three-necked bottle, 0.4 g of N-hydroxyphthalimide, 0.3 g of manganese acetate and 0.2 g of cobalt acetate are added, the temperature of a water bath is kept at 20 ℃, 5 ml/min of oxygen is introduced, magnetic stirring is started, sampling detection is carried out to monitor the complete conversion of the o-aminophenylethanol, and the introduction of the oxygen is stopped.

The reaction mixture was subjected to distillation under reduced pressure to give 10.64 g (0.0909 mol) of indole, in 90.9% molar yield and 99.1% purity.

Example 4

At room temperature, 13.7 g of o-aminophenylethanol (0.1 mol) is dissolved in 50 ml of trichloromethane in a 500 ml three-necked bottle, 0.15 g of N-hydroxyphthalimide and 0.13 g of cobalt acetate are added, the temperature is kept at 50 ℃ in a water bath, 50 ml/min of air is introduced, magnetic stirring is started, sampling detection is carried out to monitor the complete conversion of the o-aminophenylethanol, and the air introduction is stopped.

The reaction mixture was subjected to distillation under reduced pressure to give 10.66 g (0.0911 mol) of indole, in 91.1% molar yield and 99.3% purity.

Example 5

At room temperature, 13.7 g of o-aminophenylethanol (0.1 mol) is dissolved in 50 ml of trichloromethane in a 500 ml three-necked bottle, 0.2 g of N-hydroxyphthalimide and 0.3 g of cobalt acetate are added, the temperature is kept at 20 ℃ in a water bath, 50 ml/min of air is introduced, magnetic stirring is started, sampling detection is carried out to monitor the complete conversion of the o-aminophenylethanol, and the introduction of the air is stopped.

The reaction mixture was subjected to distillation under reduced pressure to give 10.67 g (0.0912 mol) of indole, in 91.2% molar yield and 99.4% purity.

The invention is not to be considered as limited to the particular embodiments shown, but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. The preparation method of the indole is characterized in that the preparation method is to synthesize the indole in one step by taking o-aminophenylethanol as a raw material through catalytic oxidation condensation, and specifically comprises the following steps:

the dosage of the catalyst is 0.02-0.08 g/g of raw materials, and the catalyst is selected from cobalt acetate, manganese acetate or a mixture of the cobalt acetate and the manganese acetate, and N-hydroxyphthalimide.

2. The method of claim 1, wherein the solvent is chloroform; the ratio of the volume of the added solvent to the molar weight of the o-aminophenylethanol is 40-60: 0.1 mL/mol.

3. The method of claim 1, wherein the catalyst is N-hydroxyphthalimide with cobalt acetate; the mass ratio of the N-hydroxyphthalimide to the cobalt acetate is 0.15-0.4: 0.1 to 0.7.

4. The method according to claim 1, wherein the reaction temperature is 30 to 40 ℃.

5. The process according to claim 1, wherein the reaction mixture is purified by distillation under reduced pressure after completion of the reaction.