A kind of green synthetic method of tetrahydro-β-carboline heterocyclic compound

A technology for green synthesis of heterocyclic compounds, applied in chemical instruments and methods, organic compounds/hydrides/coordination complex catalysts, chemical/physical processes, etc. Toxic problems, etc., to achieve the effect of easy operation, wide application range, and low requirements for reaction conditions

Active Publication Date: 2019-08-27
WENZHOU UNIVERSITY
View PDF1 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Because the Pictet-Spengler reaction mainly uses aldehydes as raw materials, and the aldehydes have a heavy odor and are highly toxic, active and unstable, and difficult to store. They need to be purified before each use, and there are many shortcomings. In addition, some methods also use transition metal catalysts and ligands, resulting in product There are heavy metal residues in the method, which is not suitable for the synthesis of pharmaceutical intermediates with high requirements on metal residues, and also limits the further synthetic application of these methods

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
  • A kind of green synthetic method of tetrahydro-β-carboline heterocyclic compound
  • A kind of green synthetic method of tetrahydro-β-carboline heterocyclic compound
  • A kind of green synthetic method of tetrahydro-β-carboline heterocyclic compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] Preparation of 1-phenyl-tetrahydro-β-carboline from tryptamine and benzyl alcohol

[0024]

[0025] Add tryptamine (0.0801g, 0.5mmol), benzyl alcohol (0.0621ml, 1.2equiv.), TEMPO (0.0234g, 30mol%), TBN (0.0176ml, 30mol%) and glacial acetic acid (0.5 ml), pumping and exchanging the gas for three times, sealing the tube with oxygen, and then reacting at 80°C for 24h under stirring. After the complete reaction was monitored by TLC, the product was separated and purified by column chromatography, and the separation yield was 82%. 1 H NMR (500MHz, DMSO-d 6 ):δ10.49(br s,1H),7.43(d,J=8.0Hz,1H),7.36-7.28(m,5H),7.24(d,J=8.0Hz,1H),7.02(t,J =7.5Hz,1H),6.96(t,J=7.5Hz,1H),5.15(s,1H),3.11-3.06(m,1H),2.98-2.94(m,1H),2.79-2.67(m, 2H), 1.87(s, 1H). 13 C NMR (125.4MHz, DMSO-d 6 ): δ142.7, 135.9, 134.9, 128.5, 128.1, 127.2, 126.8, 120.5, 118.2, 117.5, 111.0, 108.2, 56.4, 40.9, 21.9.

Embodiment 2

[0027] Preparation of 1-(4-methoxyphenyl)-tetrahydro-β-carboline from tryptamine and 4-methoxybenzyl alcohol

[0028]

[0029] In the tubular reactor, add tryptamine (0.0801g, 0.5mmol), 4-methoxybenzyl alcohol (0.0745ml, 1.2equiv.), TEMPO (0.0234g, 30mol%), TBN (0.0176ml, 30mol%) and glacial acetic acid (0.5ml), pumped and ventilated three times and sealed with oxygen, then reacted at 80°C for 24h under stirring. After the complete reaction was monitored by TLC, the product was separated and purified by column chromatography, and the separation yield was 94%. 1 H NMR (500MHz, DMSO-d 6 ): δ10.44(br s,1H),7.41(d,J=7.5Hz,1H),7.22(d,J=7.5Hz,1H),7.20(d,J=8.5Hz,2H),7.00( t,J=7.5Hz,1H),6.95(t,J=7.5Hz,1H),6.90(d,J=8.5Hz,2H),5.12(s,1H),3.73(s,3H),3.11- 3.09(m,1H),2.98-2.93(m,1H),2.79-2.66(m,2H),1.88(br s,1H). 13 C NMR (125.4MHz, DMSO-d 6 ): δ158.6, 135.9, 135.1, 134.5, 129.6, 126.8, 120.5, 118.1, 117.5, 113.5, 111.0, 108.0, 55.9, 55.1, 41.1, 21.9.

Embodiment 3

[0031] Preparation of 1-(4-methylphenyl)-tetrahydro-β-carboline from tryptamine and 4-methylbenzyl alcohol

[0032]

[0033] Add tryptamine (0.0801g, 0.5mmol) successively in the tubular reactor, 4-methylbenzyl alcohol (0.0733g, 1.2equiv.), TEMPO (0.0234g, 30mol%), TBN (0.0176ml, 30mol%) and Glacial acetic acid (0.5ml) was pumped and ventilated three times to seal the oxygen, and then reacted at 80°C for 24h under stirring. After the complete reaction was monitored by TLC, the product was separated and purified by column chromatography, and the separation yield was 89%. 1 H NMR (500MHz, DMSO-d 6 ):δ10.37(br s,1H),7.40(d,J=7.5Hz,1H),7.21(d,J=7.5Hz,1H),7.17-7.12(m,4H),6.99(t,J =7.5Hz,1H),6.94(t,J=7.5Hz,1H),5.04(s,1H),3.09-3.04(m,1H),2.94-2.89(m,1H),2.73-2.63(m, 2H), 2.28(s, 1H). 13 C NMR (125.4MHz, DMSO-d 6 ): δ140.1, 136.2, 135.9, 135.5, 128.6, 128.3, 126.8, 120.4, 118.1, 117.4, 110.9, 108.1, 56.3, 41.3, 22.2, 20.7.

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 discloses a green synthesis method of a tetrahydro-beta-pyroline heterocyclic compound. An alcohol compound is taken as a raw material, the tetrahydro-beta-porphyrin compound is obtainedthrough one-pot series reaction of a tryptamine compound and alcohol through oxidative condensation and cyclization under oxygen under the catalysis of catalysts TEMPO and TBN, the reaction temperature is 40 to 120 DEG C and the reaction time is 6 to 48 hours. The method uses the cheap, readily available, widely-sourced, stable, low-toxic and green alcohol compound as the raw material, and does not use any transition metal catalysts and ligands, and the reaction does not require protection of inert gases, is carried out under the oxygen atmosphere, takes cheap, readily available and relatively green acetic acid as a solvent, is easy to operate, and has by-products of water and no heavy metal residues in the product, thereby being green, environmentally friendly and pollution-free, so thatthe method has lower requirements on reaction conditions and wider application range, obvious advantages as compared with known methods and potential wide application prospects.

Description

technical field [0001] The invention relates to the technical field of chemical synthesis, in particular to a green synthesis method of tetrahydro-β-carboline heterocyclic compounds. Background technique [0002] The tetrahydro-β-carboline heterocyclic structure is the structural unit of many natural products and important medicines. Drugs with a tetrahydro-β-carboline heterocycle as the core structure include haimine, (+)-harmicine, (+)-yohimbine, (+)-vellosimine, Tadalafil, etc., and there are many kinds. It is well known that many molecules with a tetrahydro-β-carboline heterocycle as the core structure have biological activities such as anti-HIV, anti-tumor, and anti-malarial. Therefore, the synthesis of tetrahydro-β-carboline ring structures has always been one of the focuses of synthetic and medicinal chemists. [0003] The known synthesis methods of tetrahydro-β-carboline heterocyclic structures include traditional Pictet-Spengler condensation reaction, Graebe-Ullma...

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 Patents(China)
IPC IPC(8): C07D471/04B01J31/02
CPCC07D471/04B01J31/0235B01J35/19
Inventor 徐清刘海城
Owner WENZHOU UNIVERSITY
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