Method for preparing substituted indole-3-methanal compound

A technology of compound and compound structural formula, which is applied in the field of preparation of substituted indole-3-carboxaldehyde compounds, can solve problems such as industrialization difficulties and operational difficulties, and achieve the effects of reducing side reactions, increasing reaction yield, and reducing adsorption

Active Publication Date: 2012-10-24
上海泰坦科技股份有限公司
View PDF8 Cites 7 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Since there is a carboxyl group attached to the 2-position of the indole ring synthesized by the first two methods, a high temperature (generally above 200°C) is required to remove the carboxyl group at the 2-position, which is difficult to operate and also gives Industrialization has brought certain difficulties

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Method for preparing substituted indole-3-methanal compound
  • Method for preparing substituted indole-3-methanal compound
  • Method for preparing substituted indole-3-methanal compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] The synthesis of embodiment 1 indole-3 formaldehyde

[0031]

[0032] Add 5.6 g of 2-nitrotoluene (compound 1a, 0.041 mol) and 24.3 g of DMFDMA (0.205 mol) into 80 ml of acetonitrile, raise the reaction temperature to 85°C-95°C, and reflux for 5 hours. The reaction solution was cooled, the solvent was spin-dried, and washed with water and a small amount of ethanol to obtain 7.7 g of crude product 2a (0.0402 mol, yield 98.0%).

[0033] The obtained compound 2a was added to 130ml of methanol containing 10wt% hydrazine (hydrazine content 0.4mol, 10eq), and the temperature was raised to 50°C, reacted for 8 hours, and cooled to room temperature. The solvent was spin-dried to obtain product 3a (4.5 g, 0.0385 mol, yield 96.1%), which was dissolved in 20 ml of acetonitrile.

[0034] Add 11.2 grams of DMF (0.154mol, 4eq) and 3 grams of 4A molecular sieve into 100ml of acetonitrile, and cool the reaction to 0°C to 5°C, slowly add 11.6g of POCl dropwise under ice bath conditio...

Embodiment 2

[0037] Example 2 Synthesis of 5-fluoroindole-3-carbaldehyde

[0038]

[0039] Add 7.2 g of 5-fluoro-2-nitrotoluene (compound 1b, 0.046 mol) and 27.4 g of DMFDMA (0.232 mol) into 80 ml of acetonitrile, raise the reaction temperature to 85°C-95°C, and reflux for 5 hours. The reaction was cooled, the solvent was spin-dried, and washed with water and a small amount of ethanol to obtain 9.3 g of crude product 2b (0.0443 mol, yield 96.2%).

[0040] The obtained intermediate 2b was added to 147ml of methanol containing 10wt% hydrazine (hydrazine content 0.45mol, 10eq), and the temperature was raised to 50°C, reacted for 8 hours, and cooled to room temperature. The solvent was spin-dried to obtain 5.7 g of product 3b (0.0424 mol, yield 95.8%), which was dissolved in 20 ml of acetonitrile.

[0041] Add 12.3 grams of DMF (0.168mol, 4eq) and 3.3 grams of 4A molecular sieve into 100ml of acetonitrile, and cool the reaction to 0°C-5°C, slowly add 12.8g of POCl dropwise under ice bath c...

Embodiment 3

[0043] The synthesis of embodiment 3 6-chloroindole-3-formaldehyde

[0044]

[0045] Add 6.6 g of 4-chloro-2-nitrotoluene (compound 1c, 0.039 mol) and 23.0 g of DMFDMA (0.193 mol, 5 eq) into acetonitrile (80 ml), raise the reaction temperature to 85°C to 95°C, and reflux for 5 hours . The reaction was cooled, the solvent was spin-dried, and washed with water and a small amount of ethanol to obtain 8.4 g of crude product 2c (0.0369 mol, yield 94.6%).

[0046] The resulting intermediate 2c was added to 118ml of methanol containing 10wt% hydrazine (hydrazine content: 0.36mol, 10eq), heated to 50°C, reacted for 8 hours, and cooled to room temperature. The solvent was spin-dried to obtain 5.4 g of product 3c (0.0355 mol, yield 96.3%), which was dissolved in 20 ml of acetonitrile.

[0047] Add 10.4 grams of DMF (0.142mol, 4eq) and 3 grams of 4A molecular sieves into acetonitrile (100ml), and cool the reaction to 0°C to 5°C, slowly add 10.8g of POCl dropwise under ice bath condi...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The invention relates to the field of organic synthesis and medical intermediate preparation and especially relates to a method for preparing a substituted indole-3-methanal compound. The method comprises the following steps that N,N-dimethylformamidodimethylacetal or N,N-methylformamidodiethylacetal and substituted 2-nitrotoluene undergo a reflux reaction to produce beta-dimethylamino-2-nitrostyrene; beta-dimethylamino-2-nitrostyrene and a mixed solution of hydrazine and alcohol undergo a reaction to produce a substituted indole; and the substituted indole, dimethylformamide (DMF) and phosphorus oxyhalogen undergo a reaction to produce the substituted indole-3-methanal compound. Yields of all processes of the method provided by the invention are more than 90%. A total yield of the method is more than 80%.

Description

technical field [0001] The invention relates to the fields of organic synthesis and preparation of pharmaceutical intermediates, in particular to a preparation method of substituted indole-3-carboxaldehyde compounds. Background technique [0002] Substituted indole-3-carbaldehyde compounds are an important class of intermediates in organic synthetic chemistry, such as indole-3-carbaldehyde (CAS 487-89-8), 5-fluoroindole-3-carbaldehyde (CAS 2338- 71-8), 6-fluoroindole-3-carbaldehyde (CAS 2795-41-7), 6-chloroindole-3-carbaldehyde (CAS 703-82-2), 5-methoxyindole-3 -Formaldehyde (CAS 10601-19-1), has a wide range of uses: it is used to synthesize some tryptamines and their derivatives with pharmaceutical activity; to synthesize some tryptophan compounds; to synthesize some plant growth regulators, such as indole- 3-acetonitrile and indole-3-acetic acid compounds; synthesis of various biologically active pharmaceutical intermediates. Therefore, the synthetic method of substitut...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Applications(China)
IPC IPC(8): C07D209/12
Inventor 谢应波张庆张华姚为建
Owner 上海泰坦科技股份有限公司
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap