CN117924143A - Preparation method of 5, 6-dihydroxyindole - Google Patents

Preparation method of 5, 6-dihydroxyindole Download PDF

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CN117924143A
CN117924143A CN202410087008.XA CN202410087008A CN117924143A CN 117924143 A CN117924143 A CN 117924143A CN 202410087008 A CN202410087008 A CN 202410087008A CN 117924143 A CN117924143 A CN 117924143A
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dihydroxyindole
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dibenzyloxybenzaldehyde
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宋也
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Beijing Chengyu Specialty Chemical Co ltd
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Abstract

The invention belongs to the field of chemical intermediate preparation, and particularly relates to a preparation method of 5, 6-dihydroxyindole, which is implemented according to the following steps: (1) Nitrifying 3, 4-dibenzyloxybenzaldehyde by a solid nitrifier to obtain 2-nitro-4, 5-dibenzyloxybenzaldehyde; (2) Performing condensation reaction on the nitrified product obtained in the step (1) and nitromethane to obtain 2, beta-dinitro-4, 5-dibenzyloxy styrene; (3) Adding a catalyst into a reaction system, and obtaining a target product 5, 6-dihydroxyindole through reduction, intramolecular cyclization and debenzylation tandem reaction. The synthesis method has the characteristics of readily available raw materials, good reaction selectivity, high purity, good yield, mild reaction conditions, easy separation of products, environmental friendliness and the like, and is suitable for industrial production.

Description

Preparation method of 5, 6-dihydroxyindole
Technical Field
The invention belongs to the field of chemical intermediate preparation, and particularly relates to a preparation method of 5, 6-dihydroxyindole.
Background
The 5, 6-dihydroxyindole is an important intermediate of melanin, is also an intermediate of amino acid, alkaloid and tryptamine, has better effect on dyeing keratin fibers, can be compatible with isatin, and can be used as a hair dye for oxidation or a matched dye. The biological agent can be converted into chemical substances contained in human bodies in a biological mode, so that the biological agent has extremely high safety. Are currently used in some washing products to replace aniline, phenolic compounds (WO 2006/062070; WO 2007/141919). The 5, 6-dihydroxyindole is used in hair dye formulas and also in hair care and styling shampoos. In recent years, it has been found to have a bactericidal effect and can be used as a preservative and bactericide for wood storage.
Based on the good effect of 5, 6-dihydroxyindole on hair dye, preservative and antioxidant application, the world large cosmetic companies such as Europea, baojie, kaowang and the like have started to apply 5, 6-dihydroxyindole and related products thereof in the early 90 th century. However, no report on mass production of the substance is available in the world so far, and the main problem is that the 5, 6-dihydroxyindole has strict requirements on synthetic environment and the quality of the product is difficult to control.
In early synthetic studies [(1)Mason,H.S.J.Biol.Chem.1948,172,83;(2)Pawelek,J.;Lerner,A.B.;Nature,1978,276,627;(3)Beer,R.J.S.;Clarke,K.;Khorana,H.G.;Robertson,A.J.Chem.Soc.1948,2223] reported that 5, 6-dihydroxyindole was obtained by oxidative cyclization by biosynthetic methods starting from dopamine (3, 4-dihydroxyphenethylamine) and its derivatives.
The method realizes the synthesis of 5, 6-dihydroxyindole by virtue of the oxidation-reduction characteristic of the ortho-dihydroxyl of the dopamine intermediate and through intramolecular cyclization of phenethylamine. However, the raw materials of dopamine are poor in stability and high in price, are limited by raw material sources, and cannot meet the requirement of mass production.
In literature [(1)Benigni,J.D.;Minnis,R.L.The synthesis of 5,6-dihydroxyindole and some of its derivatives,J.Heterocyclic.Chem.1965,2(4),387-392;(2)Process for preparing5,6-dihydroxyindole.US 4595765], 3, 4-dihydroxybenzaldehyde is used as a starting material, and is subjected to benzyl protection, condensation and nitration of hydroxyl groups to form 2, beta-dinitrostyrene, and then deprotection and hydrogenation reduction cyclization to obtain 5, 6-dihydroxyindole. Concentrated nitric acid is used as the nitrating agent in the nitration process, and a large amount of trifluoroacetic acid is used in the deprotection process. The use of strong acid has high requirements on equipment in the reaction process, and meanwhile, the use of a large amount of strong acid brings inconvenience to subsequent treatment, so that a large amount of industrial waste is generated, environmental pollution is caused, and the large-scale production is not facilitated.
In addition, the patent also discloses that piperonal is used as a raw material, and the reaction of introducing hydroxyl protecting groups is omitted, but the raw material is suddenly toxic, the operation difficulty is great, and batch preparation cannot be realized.
In literature (Murphy,B.P.;Banks,H.D.Synthesis of5,6-dihydroxy indole:A novel reductive cyclization of(E)-4,5-dihydroxy-2,β-dinitro-styrene.Synth.Commun.1985,(15):321-329), vanillin is used as a raw material, and the introduction of methoxy as a hydroxyl protecting group brings great problems to the subsequent deprotection process, and becomes a potential safety hazard.
As an improvement of the above process, document (Novellino,L.;Ischia,M.;Prota,G.Expedient Synthesis of 5,6-Dihydroxyindole and Derivatives via an Improved Zn(II)-Assisted 2,β-Dinitrostyrene Approach,Synthesis,1999,793-796) reports that the nitration and reductive cyclization process is directly carried out by 3, 4-dihydroxybenzaldehyde without hydroxyl protection, but the reaction uses tetranitromethane in the nitration process, which has the problem of use safety; the reduction process uses a large amount of sodium hydrosulfite and zinc salt, which causes great three-waste problem for subsequent treatment.
Among the prior synthesis methods disclosed and reported, the relatively mature synthesis method is a method using 3, 4-dimethoxybenzyl cyanide as a raw material [ (1) 5, 6-dihydroxyindole and 3-alkyl derivatives and intermediate compounds thereof, ], CN 87107372A; (2) The preparation method comprises the steps of (1) synthesizing effective army, sun Shujuan, chen, feng Cheng, 5, 6-dihydroxyindole, fuel and dyeing, 2007,4 (1), 47-49], and carrying out demethylation to obtain an intermediate 3, 4-dihydroxyphenylacetonitrile; then 3, 4-dibenzyloxy benzyl cyanide is obtained through benzyl protection; 2-nitro-3, 4-dibenzyloxy benzyl cyanide is obtained through nitration; then the 3, 4-dibenzyloxy indole is obtained through a reductive cyclization reaction, and finally the protecting group is removed to obtain the 5, 6-dihydroxyindole. The nitrifying reaction process has the problem of safety risk caused by the accumulation of the exothermic amount of the nitrifying reaction. The reaction process is longer, so that the problems of high batch preparation production cost, large wastewater production and the like are caused.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide the preparation method of the 5, 6-dihydroxyindole, which has the advantages of easily available reaction raw material sources, easily controllable conditions, good selectivity, high yield and simple and convenient operation process.
In order to solve the technical problems, the invention is realized as follows:
The preparation method of the 5, 6-dihydroxyindole comprises the following steps:
(1) Nitrifying 3, 4-dibenzyloxybenzaldehyde by a solid nitrifier to obtain 2-nitro-4, 5-dibenzyloxybenzaldehyde;
(2) Performing condensation reaction on the nitrified product obtained in the step (1) and nitromethane to obtain 2, beta-dinitro-4, 5-dibenzyloxy styrene;
(3) Adding a catalyst into a reaction system, and obtaining a target product 5, 6-dihydroxyindole through reduction, intramolecular cyclization and debenzylation tandem reaction.
As a preferred embodiment, in the step (1), 3, 4-dibenzyloxybenzaldehyde is nitrified by a solid nitrifying agent in glacial acetic acid.
Further, the solid nitrifying agent is one or a mixture of more than two of urea nitrate, thiourea nitrate, guanidine nitrate or melamine nitrate.
Further, in the step (1), the nitration reaction temperature is-20-40 ℃.
Further, in the step (2), ammonium formate is used as a reaction medium, and the nitrified product obtained in the step (1) is subjected to condensation reaction with nitromethane in the ammonium formate.
Further, the ammonium formate salt is one or a mixture of more than two of formic acid-ethanolamine, formic acid-diethanolamine, formic acid-triethanolamine or formic acid-triethylamine.
Further, in the step (2), the condensation reaction temperature is 20 to 120 ℃.
Further, in the step (3), the palladium-carbon catalyst is used in an amount of 0.5 to 30% by weight of the beta-dinitrostyrene.
Further, in the step (3), the temperature of the series reaction is 20-120 ℃.
Further, in the step (3), a palladium-carbon catalyst is added into a reaction system, and the target product 5, 6-dihydroxyindole is obtained through reduction, intramolecular cyclization and debenzylation tandem reaction.
The synthesis method of 5, 6-dihydroxyindole takes 3, 4-dibenzyloxybenzaldehyde as a raw material, and the raw material is subjected to nitration reaction by a solid nitrating agent to obtain 2-nitro-4, 5-dibenzyloxybenzaldehyde; and condensing the nitrified product with nitromethane in ammonium formate to obtain 2, beta-dinitro-4, 5-dibenzyloxy styrene, adding a palladium-carbon catalyst into the reaction, and carrying out serial reactions of reduction, intramolecular cyclization and debenzylation to realize the synthesis of 5, 6-dihydroxyindole.
The specific reaction principle is as follows:
The synthesis of 2-nitro-4, 5-dibenzyloxybenzaldehyde in step 1) is prepared by nitrifying 3, 4-dibenzyloxybenzaldehyde in glacial acetic acid by a solid nitrifying agent. The solid nitrating agent is urea nitrate, thiourea nitrate, guanidine nitrate or melamine nitrate, preferably urea nitrate or thiourea nitrate. The reaction temperature is-20 to 40 ℃, preferably-10 to 30 ℃.
In the step 2), the synthesis of the 2, beta-dinitro-4, 5-dibenzyloxy styrene is carried out by taking ammonium formate as a reaction medium and reacting 2-nitro-4, 5-dibenzyloxy benzaldehyde with nitromethane. The ammonium formate salt is formic acid-ethanolamine, formic acid-diethanolamine, formic acid-triethanolamine or formic acid-triethylamine, preferably formic acid-ethanolamine or formic acid-diethanolamine. The reaction temperature is 20 to 120℃and preferably 30 to 100 ℃.
Finally, after the synthesis reaction of the 2, beta-dinitro-4, 5-dibenzyloxy styrene is finished, a palladium-carbon catalyst is directly added into the reaction system, and the synthesis of the 5, 6-dihydroxyindole is realized through the serial reaction of reduction, intramolecular cyclization and debenzylation. The catalyst is used in an amount of 0.5 to 30% by weight, preferably 1 to 20% by weight, based on the weight of the beta-dinitrostyrene. The reaction temperature is20 to 100℃and preferably 30 to 80 ℃.
The basic raw materials 3, 4-dibenzyloxybenzaldehyde related by the invention can be prepared by researching synthesis of easily-obtained raw materials 3, 4-dihydroxyformaldehyde and benzyl chloride under mild reaction conditions by referring to the prior literature methods [ (1) Zhang Qunzheng, dong Yan, south She Fei, cai Xuediao, zheng Xiaohui, beta- (3, 4-dihydroxyphenyl) -alpha-isopropyl hydroxy propionate/borneol ester and organic chemistry ,2009,29(9),1466-1469;(2)Ramage,R.;Griffiths,G.J.;Shutt,F.E.;Sweeney,J.N.A.Dioxolanones as synthetic intermediates.Part 2.Synthesis of tetronic acids and pulvinones,J.Chem.Soc.Perkin Trans.1,1984,1539-1545]. Ammonium formate salts can be prepared by readily available starting materials, reference methods [(1)Suzuki,H.;Yoshioka,S.;Igesaka A.;Nishioka,H.;Takeuchi,Y.Palladium-catalyzed hydrogenation with use of ionic liquid bis(2-hydroxyethyl)ammonium formate[BHEA][HCO2]as a solvent and hydrogen source,Tetrahedron,2013,69(13),6399-6403;(2)Sekiya,M.;Suzuki,K.Formic Acid Reduction.VII.Reduction of Carbon-Carbon Double Bonds adjacent to Carbonyls,Chem.Pharm.Bull.1970,18(8),1530-1534.
The invention has the advantages of easily obtained reaction raw material sources, easily controlled conditions, good selectivity, high yield and simple and convenient operation process, and compared with the prior art, the invention has the following characteristics:
(1) The synthesis method of 5, 6-dihydroxyindole provided by the invention can meet the requirements of high purity and high efficiency in the fields of chemical industry, medicine and the like.
(2) The 5, 6-dihydroxyindole obtained by the method is white-like crystal, and the purity is more than 99.5%.
(3) The synthesis process of the 5, 6-dihydroxyindole provided by the invention is simple and convenient to operate, raw materials are easy to obtain, production is safe, and large-scale production is facilitated.
Detailed Description
The invention will be further described with reference to specific examples, but the invention is not limited to these examples.
Example 1
1) Preparation of 2-nitro-4, 5-dibenzyloxybenzaldehyde
3, 4-Dibenzyloxybenzaldehyde (31.8 g,0.1 mol) and acetic acid (150 mL) were added to a 500mL three-necked flask under vigorous stirring, urea nitrate (14.8 g,0.12 mol) was added in portions under cooling, the reaction was carried out at 15℃for 2 hours (the end point of the reaction was determined by thin layer chromatography) after the addition, the reaction solution was slowly poured into ice water (300 mL) under stirring, the precipitated precipitate was filtered, the filter cake was washed with water to neutrality, dried, and recrystallized from absolute ethanol to give 34.1g of a product, yield: 94%.
Melting point: 153-154 ℃.
1HNMR(400MHz,CDCl3),5.26(2H,s),5.39(2H,s),7.12(1H,s),7.43～7.65(10H,m),7.89(1H,s),9.92(1H,s).
2) Preparation of 5, 6-dihydroxyindole
(1) Synthesis of 2, beta-dinitro-4, 5-dibenzyloxy styrene
2-Nitro-4, 5-dibenzyloxybenzaldehyde (72.6 g,0.2 mol), formic acid-ethanolamine (150 g), nitromethane (18.3 g,0.3 mol) were each added to a 500mL three-necked flask at room temperature, and the mixture was heated to 80℃with stirring, reacted at room temperature for 5 hours (TLC (termination of reaction was determined by thin layer chromatography), and then cooled to 20 ℃.
(2) Synthesis of 5, 6-dihydroxyindole
To the above reaction mixture was added 10% Pd/C (10 g) catalyst, slowly heated to 50℃and maintained for reaction for 6 hours (end point of reaction was determined by thin layer chromatography), cooled to 20℃and the reaction solution was transferred into water (200 ml). Filtering (recovering catalyst), extracting with isopropyl ether (2×100 ml), decolorizing the extractive solution with active carbon, and evaporating to dryness to obtain white crystalline product. Recrystallization from isopropyl ether-n-hexane gave 22.5g of white crystals in 76% yield. Melting point: 142-142.5 ℃.
1H NMR(400MHz,DMSO-d6)：5.12-5.32(2H,m),6.52 -6.78(3H,m),6.91(1H,d),7.05(1H,s),9.87(1H,s).
The purity of the product is 99.85% by liquid chromatography.
Example 2
1) Preparation of 2-nitro-4, 5-dibenzyloxybenzaldehyde
3, 4-Dibenzyloxybenzaldehyde (31.8 g,0.1 mol) and acetic acid (120 mL) were added to a 500mL three-necked flask under vigorous stirring, urea nitrate (18.5 g,0.15 mol) was added in portions under cooling, the reaction was completed at 20℃for 1.5 hours (the end point of the reaction was determined by thin layer chromatography), the reaction solution was slowly poured into ice water (300 mL) under stirring, the precipitated precipitate was filtered, the filter cake was washed with water to neutrality, dried, and methanol was recrystallized to give 33.4g of a product, yield: 92%.
Melting point: 153-154 ℃.
2) Preparation of 5, 6-dihydroxyindole
(1) Synthesis of 2, beta-dinitro-4, 5-dibenzyloxy styrene
2-Nitro-4, 5-dibenzyloxybenzaldehyde (72.6 g,0.2 mol), formic acid-diethanolamine (120 g), nitromethane (18.3 g,0.3 mol) were added to 500mL three-necked flask at room temperature, and the mixture was heated to 70℃with stirring, reacted at room temperature for 6 hours (TLC (end point of reaction was determined by thin layer chromatography), and then cooled to 20 ℃.
(2) Synthesis of 5, 6-dihydroxyindole
To the above reaction mixture was added 10% Pd/C (10 g) catalyst, slowly heated to 60℃and maintained for 4 hours (end point of reaction was determined by thin layer chromatography), cooled to 20℃and the reaction solution was added to water (200 ml). Filtering (recovering catalyst), extracting with isopropyl ether (2×100 ml), decolorizing the extractive solution with active carbon, and evaporating to dryness to obtain white crystalline product. Recrystallization from isopropyl ether-n-hexane gave 23.2g of white crystals in 78% yield. Melting point: 142-143 ℃.
The purity of the product is 99.57 percent by liquid chromatography.
Example 3
1) Preparation of 2-nitro-4, 5-dibenzyloxybenzaldehyde
3, 4-Dibenzyloxybenzaldehyde (31.8 g,0.1 mol) and acetic acid (150 mL) were added to a 500mL three-necked flask under vigorous stirring, guanidine nitrate (18.3 g,0.15 mol) was added in portions under cooling, the reaction was completed at 15℃for 3 hours (the end of the reaction was determined by thin layer chromatography), the reaction solution was slowly poured into ice water (300 mL) under stirring, the precipitated precipitate was filtered, the filter cake was washed with water to neutrality, dried, and recrystallized from absolute ethanol to give 34.8g of the product, yield: 95%.
Melting point: 153-154 ℃.
2) Preparation of 5, 6-dihydroxyindole
(1) Synthesis of 2, beta-dinitro-4, 5-dibenzyloxy styrene
2-Nitro-4, 5-dibenzyloxybenzaldehyde (72.6 g,0.2 mol), formic acid-ethanolamine (140 g) and nitromethane (24.4 g,0.4 mol) were each added to 500mL three-necked flask at room temperature, and the mixture was heated to 60℃under stirring, reacted under heat preservation for 8 hours (TLC (termination point of reaction was determined by thin layer chromatography), and then cooled to 20 ℃.
(2) Synthesis of 5, 6-dihydroxyindole
To the above reaction mixture was added 10% Pd/C (8 g) catalyst, slowly heated to 50℃and maintained for 7 hours (end point of reaction was determined by thin layer chromatography), cooled to 20℃and the reaction solution was transferred into water (200 ml). Filtering (recovering catalyst), extracting with isopropyl ether (2×100 ml), decolorizing the extractive solution with active carbon, and evaporating to dryness to obtain white crystalline product. Recrystallization from isopropyl ether-n-hexane gave 22.2g of white crystals in 75% yield. Melting point: 142-143 ℃.
The purity of the product is 99.65% by liquid chromatography.
Example 4
1) Preparation of 2-nitro-4, 5-dibenzyloxybenzaldehyde
3, 4-Dibenzyloxybenzaldehyde (159 g,0.5 mol) and acetic acid (600 mL) were added to a 1000mL three-necked flask under vigorous stirring, guanidine nitrate (85.4 g,0.7 mol) was added in portions under cooling, the reaction was completed at 15℃for 4 hours (the end point of the reaction was determined by thin layer chromatography), the reaction solution was slowly poured into ice water (1200 mL) under stirring, the precipitated precipitate was filtered, the filter cake was washed with water to neutrality, dried, and recrystallized from absolute ethanol to give 168.8g of the product, yield: 93%.
Melting point: 153-154 ℃.
2) Preparation of 5, 6-dihydroxyindole
(1) Synthesis of 2, beta-dinitro-4, 5-dibenzyloxy styrene
2-Nitro-4, 5-dibenzyloxybenzaldehyde (181.5 g,0.5 mol), formic acid-ethanolamine (300 g), nitromethane (45.8 g,0.75 mol) were added to 500mL three-necked flask at room temperature, and the mixture was heated to 60℃with stirring, reacted under heat preservation for 8 hours (TLC (the reaction end point was determined by thin layer chromatography), and then cooled to 20 ℃.
(2) Synthesis of 5, 6-dihydroxyindole
To the above reaction mixture was added 10% Pd/C (20 g) catalyst, slowly heated to 50℃and maintained for 5 hours (end point of reaction was determined by thin layer chromatography), cooled to 20℃and the reaction solution was poured into water (1200 ml). Filtering (recovering catalyst), extracting with isopropyl ether (2×400 ml), decolorizing the extractive solution with active carbon, and evaporating to dryness to obtain white crystalline product. Recrystallization from isopropyl ether-n-hexane gave 53.6g of white crystals in a yield of 72%. Melting point: 142-143 ℃.
The purity of the product is 99.81% by liquid chromatography.
Example 5
1) Preparation of 2-nitro-4, 5-dibenzyloxybenzaldehyde
3, 4-Dibenzyloxybenzaldehyde (159 g,0.5 mol) and acetic acid (700 mL) were added to a 1000mL three-necked flask under vigorous stirring, urea nitrate (98.3 g,0.8 mol) was added in portions under cooling, the reaction was completed at 10℃for 5 hours (the end point of the reaction was determined by thin layer chromatography), the reaction solution was slowly poured into ice water (1500 mL) under stirring, the precipitated precipitate was filtered, the filter cake was washed with water to neutrality, dried, and methanol was recrystallized to give 165.2g of the product, yield: 91%.
Melting point: 153-154 ℃.
2) Preparation of 5, 6-dihydroxyindole
(1) Synthesis of 2, beta-dinitro-4, 5-dibenzyloxy styrene
2-Nitro-4, 5-dibenzyloxybenzaldehyde (181.5 g,0.5 mol), formic acid-diethanolamine (400 g), nitromethane (36.6 g,0.6 mol) were added to 500mL three-necked flask at room temperature, and the mixture was heated to 70℃with stirring, reacted at room temperature for 10 hours (TLC (end point of reaction was determined by thin layer chromatography), and then cooled to 20 ℃.
(2) Synthesis of 5, 6-dihydroxyindole
To the above reaction mixture was added 10% Pd/C (25 g) catalyst, slowly heated to 50℃and maintained for 4 hours (end point of reaction was determined by thin layer chromatography), cooled to 20℃and the reaction solution was transferred into water (1000 ml). Filtering, extracting with isopropyl ether (2×400 ml), decolorizing the extractive solution with active carbon, and evaporating to dryness to obtain white crystalline product. Recrystallization from isopropyl ether-n-hexane gave 52.2g of white crystals in a yield of 70%. Melting point: 142-143 ℃.
The purity of the product is 99.72 percent by liquid chromatography.
The foregoing is merely illustrative and explanatory of the invention as it is claimed, as modifications and additions may be made to, or similar to, the particular embodiments described, without the benefit of the inventors' inventive effort, and as alternatives to those of skill in the art, which remain within the scope of this patent.

Claims (10)

1. The preparation method of the 5, 6-dihydroxyindole is characterized by comprising the following steps:
(1) Nitrifying 3, 4-dibenzyloxybenzaldehyde by a solid nitrifier to obtain 2-nitro-4, 5-dibenzyloxybenzaldehyde;
(2) Performing condensation reaction on the nitrified product obtained in the step (1) and nitromethane to obtain 2, beta-dinitro-4, 5-dibenzyloxy styrene;
(3) Adding a catalyst into a reaction system, and obtaining a target product 5, 6-dihydroxyindole through reduction, intramolecular cyclization and debenzylation tandem reaction.
2. The process for preparing 5, 6-dihydroxyindole according to claim 1, wherein: in step (1), 3, 4-dibenzyloxybenzaldehyde is nitrated in glacial acetic acid by a solid nitrating agent.
3. The process for preparing 5, 6-dihydroxyindole according to claim 2, wherein: the solid nitrifying agent is one or a mixture of more than two of urea nitrate, thiourea nitrate, guanidine nitrate or melamine nitrate.
4. A process for the preparation of 5, 6-dihydroxyindole according to claim 3, wherein: in the step (1), the nitration reaction temperature is-20-40 ℃.
5. The process for preparing 5, 6-dihydroxyindole according to claim 4, wherein: in the step (2), ammonium formate is used as a reaction medium, and the nitrified product obtained in the step (1) is subjected to condensation reaction with nitromethane in the ammonium formate.
6. The process for preparing 5, 6-dihydroxyindole according to claim 5, wherein: the ammonium formate salt is one or more than two of formic acid-ethanolamine, formic acid-diethanolamine, formic acid-triethanolamine or formic acid-triethylamine.
7. The process for preparing 5, 6-dihydroxyindole according to claim 6, wherein: in the step (2), the condensation reaction temperature is 20-120 ℃.
8. The process for preparing 5, 6-dihydroxyindole according to claim 7, wherein: in the step (3), the dosage of the palladium-carbon catalyst is 0.5-30% of the weight of the beta-dinitrostyrene.
9. The process for preparing 5, 6-dihydroxyindole according to claim 7, wherein: in the step (3), the temperature of the tandem reaction is 20-120 ℃.
10. The process for preparing 5, 6-dihydroxyindole according to claim 9, wherein: in the step (3), a palladium-carbon catalyst is added into a reaction system, and the target product 5, 6-dihydroxyindole is obtained through reduction, intramolecular cyclization and debenzylation tandem reaction.
CN202410087008.XA 2024-01-22 2024-01-22 Preparation method of 5, 6-dihydroxyindole Pending CN117924143A (en)

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