Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

3-diaryl methane-4-hydroxycoumarin derivative preparation method

A technology of hydroxycoumarin and diarylmethane, which is applied in the field of preparation of 3-diarylmethane-4-hydroxycoumarin derivatives, can solve unfavorable environmental protection and industrialized production, poor regioselectivity, and reaction conditions harsh problems

Inactive Publication Date: 2017-07-21
CHINA PHARM UNIV
View PDF0 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although the existing methods can obtain the target product, there are still many disadvantages: such as the use of expensive transition metals, not only the cost is high, but also the problem of metal residue environmental pollution; harsh reaction conditions such as high temperature and strong acid; poor regioselectivity; a large amount of waste will be generated
These shortcomings are not conducive to environmental protection and industrial production, so it is of great research value to develop a simple and effective synthetic method to construct 3-diarylmethane-4-hydroxycoumarin derivatives

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
  • 3-diaryl methane-4-hydroxycoumarin derivative preparation method
  • 3-diaryl methane-4-hydroxycoumarin derivative preparation method
  • 3-diaryl methane-4-hydroxycoumarin derivative preparation method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0016] 3-((3,5-di-tert-butyl-4-hydroxyphenyl)(4-methylphenyl)methyl)-4-hydroxycoumarin (1)

[0017]

[0018] Take a reaction tube, add 2,6-di-tert-butyl-4-(4-methylbenzylidene)cyclohexa-2,5-dienone (61mg, 0.2mmol, 1.0equiv), 4-hydroxy Coumarin (38mg, 0.24mmol, 1.2equiv), boron trifluoride diethyl ether (0.04mmol, 0.2equiv), 1mL of dichloromethane, reacted at room temperature for 24 hours, evaporated the solvent under reduced pressure and separated through a silica gel column to obtain White solid product 84mg, yield 90%.

[0019] 1 H NMR (300MHz, CDCl 3 )δ7.76(d, J=8.0Hz, 1H), 7.53(t, J=7.8Hz, 1H), 7.38-7.22(m, 2H), 7.18(s, 4H), 7.08(s, 2H), 6.58(s, 1H), 5.85(s, 1H), 5.30(s, 1H), 2.35(s, 3H), 1.38(s, 18H)ppm; 13 C NMR (75MHz, CDCl 3 )δ163.4, 160.6, 153.4, 152.7, 137.5, 137.1, 137.0, 131.9, 130.4, 129.8, 128.6, 125.4, 123.9, 123.1, 116.4, 116.1, 108.3, 46.9, 34.5, 30.2, 21.1ppm; m / z 471.2[M+H] + ; m.p.202-204°C.

Embodiment 2

[0021] 3-((3,5-di-tert-butyl-4-hydroxyphenyl)(4-methoxyphenyl)methyl)-4-hydroxycoumarin (2)

[0022]

[0023] Take a reaction tube, add 2,6-di-tert-butyl-4-(4-methoxybenzylidene)cyclohexa-2,5-dienone (64mg, 0.2mmol, 1.0equiv), 4- Hydroxycoumarin (38mg, 0.24mmol, 1.2equiv), boron trifluoride diethyl ether (0.04mmol, 0.2equiv), 1mL dichloromethane, reacted at room temperature for 24 hours, evaporated the solvent under reduced pressure and separated by silica gel column 85 mg of white solid product was obtained with a yield of 87%.

[0024] 1 H NMR (300MHz, CDCl 3 )δ7.74(d, J=7.9Hz, 1H), 7.52(t, J=7.7Hz, 1H), 7.40-7.14(m, 4H), 7.06(s, 2H), 6.90(d, J=8.2 Hz, 2H), 6.58(s, 1H), 5.81(s, 1H), 5.30(s, 1H), 3.80(s, 3H), 1.37(s, 18H)ppm; 13 C NMR (75MHz, CDCl 3 )δ163.4, 160.6, 158.8, 153.4, 152.7, 137.1, 132.4, 131.9, 130.6, 129.8, 125.4, 123.9, 123.1, 116.4, 116.1, 114.5, 108.3, 55.3, 46.5, 34.5, 30.2ppm; m / z 487.2[M+H] + ; m.p.217-218℃.

Embodiment 3

[0026] 3-((3,5-di-tert-butyl-4-hydroxyphenyl)(4-fluorophenyl)methyl)-4-hydroxycoumarin (3)

[0027]

[0028] Take a reaction tube, add 2,6-di-tert-butyl-4-(4-fluorobenzylidene)cyclohexa-2,5-dienone (62mg, 0.2mmol, 1.0equiv), 4-hydroxy Soybean (38mg, 0.24mmol, 1.2equiv), boron trifluoride ethyl ether (0.04mmol, 0.2equiv), 1mL dichloromethane, reacted at room temperature for 24 hours, evaporated the solvent under reduced pressure and separated through silica gel column to obtain The pink solid product is 82mg, and the yield is 86%.

[0029] 1 H NMR (300MHz, CDCl 3 )δ7.72(d, J=7.9Hz, 1H), 7.53(t, J=7.7Hz, 1H), 7.40-7.14(m, 4H), 7.04(t, J=8.2Hz, 4H), 6.52( s, 1H), 5.80 (s, 1H), 5.31 (s, 1H), 1.34 (s, 18H) ppm; 13 CNMR (75MHz, CDCl 3 )δ163.6, 160.8, 153.7, 152.7, 137.5, 136.0, 132.1, 130.4, 130.3, 125.3, 123.9, 123.2, 116.5, 116.0, 115.9, 115.6, 107.7, 46.7, 34.5, 30.1ppm; MS (ESI) z 475.2[M+H] + ; m.p.225-227℃.

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 chemical synthetic methodology, in particular to a 3-diaryl methane-4-hydroxycoumarin derivative preparation method. The method includes: directly taking 2,6-ditert-butyl-4-benzal hexanaphthene-2,5-dienone derivatives and substituted 4-hydroxycoumarin as substrates, taking methylene dichloride as a solvent, performing room-temperature reaction for 24h under the condition that boron trifluoride diethyl etherate serves as a catalyst, and adopting 1,6-addition reaction for synthesis to obtain 3-diaryl methane-4-hydroxycoumarin derivatives. The method has advantages of wide substrate applicability, high yield, mild conditions, easiness in raw material acquisition, simplicity in operation, environmental friendliness, high atom economy and the like.

Description

technical field [0001] The invention relates to a preparation method of 3-diarylmethane-4-hydroxycoumarin derivatives, belonging to the field of organic chemistry synthesis methodology. Background technique [0002] The coumarin skeleton currently exists in a variety of natural products and drug molecules with biological activity, especially 4-hydroxycoumarin and its derivatives are important raw materials for the synthesis of natural products and drug molecules. For example, warfarin produced by the reaction of 4-hydroxycoumarin and unsaturated ketone is a widely used anticoagulant drug; Tioclomarol is a second-generation insecticide drug derived from 4-hydroxycoumarin, which can effectively control pests In addition, many natural products composed of coumestan also contain coumarin skeletons, so it is of great significance to develop simple and effective synthetic methods to construct functionalized coumarins. In recent years, the diaryl methylation at the C3 position of ...

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
IPC IPC(8): C07D311/56
CPCC07D311/56
Inventor 姚和权许秀艳章凯帆
Owner CHINA PHARM UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com