Preparation method of (S)-(+)-3,4,8,8a-tetrahydro-8a-methyl-1,6-(2H,7H)-naphthoquinone

A technology of methyl and naphthoquinone, which is applied in the field of -3, can solve the problems of discomfort, mediocre catalytic effect, and difficulty in catalyst synthesis, and achieve the effects of low dosage, excellent stereoselectivity, and excellent catalytic ability

Inactive Publication Date: 2019-02-22
中国人民解放军军事科学院防化研究院
View PDF0 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Many structures have been reported as chiral catalysts for this reaction, but these catalysts are often difficult to synthesize or have general catalytic effects, and are not suitable for (S)-(+)-3,4,8,8a-tetrahydro-8a-methanol Rapid and Massive Preparation of 1,6-(2H,7H)-Naphthoquinone

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
  • Preparation method of (S)-(+)-3,4,8,8a-tetrahydro-8a-methyl-1,6-(2H,7H)-naphthoquinone
  • Preparation method of (S)-(+)-3,4,8,8a-tetrahydro-8a-methyl-1,6-(2H,7H)-naphthoquinone
  • Preparation method of (S)-(+)-3,4,8,8a-tetrahydro-8a-methyl-1,6-(2H,7H)-naphthoquinone

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0022] In a 100mL flask, 71.61mmol of I, 0.5mol% of L-prolinamide compound III and 1.79mmol of benzoic acid were mixed uniformly, stirred at 20°C for 4 days, and the system turned black. Afterwards, the reaction solution was transferred to a 250 mL round-bottomed flask with 100 mL of ethyl acetate, and the organic phase was washed with 30 mL of saturated sodium bicarbonate and 30 mL of saturated brine, respectively, and dried over anhydrous sodium sulfate. Afterwards, 3 g of activated carbon (100 mesh) was added to the organic phase, stirred at 20° C. for 15 hours, and filtered under normal pressure. The filtrate was precipitated under reduced pressure, and the residue was dissolved in 10 mL of methyl tert-butyl ether, frozen at -25°C for 24 hours, and filtered to obtain the precipitated brown solid, namely (S)-(+)-3,4,8,8a -Tetrahydro-8a-methyl-1,6-(2H,7H)-naphthoquinone (II), yield 86%, ee=99%.

example 2

[0024] In a 500mL flask, 572.88mmol (112.42g) of I, 0.5mol% of L-prolinamide compound III and 14.32mmol of benzoic acid were mixed uniformly, stirred at 20°C for 5 days, and the system turned black. Afterwards, the reaction solution was transferred to a 2000 mL round-bottomed flask with 800 mL of ethyl acetate, and the organic phase was washed with 240 mL of saturated sodium bicarbonate and 240 mL of saturated brine, respectively, and dried over anhydrous sodium sulfate. Afterwards, 24 g of activated carbon (100 mesh) was added to the organic phase, stirred at 20° C. for 15 hours, and filtered under normal pressure. The filtrate was precipitated under reduced pressure, and the residue was dissolved in 80 mL of methyl tert-butyl ether, frozen at -25°C for 24 hours, and filtered to obtain the precipitated brown solid, namely (S)-(+)-3,4,8,8a -Tetrahydro-8a-methyl-1,6-(2H,7H)-naphthoquinone (II), yield 82%, ee=99%.

example 3

[0026]In a 100mL flask, 71.61mmol of I, 1.0mol% of L-proline amide compound III and 1.79mmol of benzoic acid were mixed uniformly, and reacted for 4 hours under 5W microwave radiation conditions, and the temperature of the control system was not more than 45°C. The color becomes darker. Afterwards, the reaction solution was transferred to a 250 mL round-bottomed flask with 100 mL of ethyl acetate, and the organic phase was washed with 30 mL of saturated sodium bicarbonate and 30 mL of saturated brine, respectively, and dried over anhydrous sodium sulfate. Afterwards, 3 g of activated carbon (100 mesh) was added to the organic phase, stirred at 20° C. for 15 hours, and filtered under normal pressure. The filtrate was precipitated under reduced pressure, and the residue was dissolved in 10 mL of methyl tert-butyl ether, frozen at -25°C for 24 hours, and filtered to obtain the precipitated brown solid, namely (S)-(+)-3,4,8,8a -Tetrahydro-8a-methyl-1,6-(2H,7H)-naphthoquinone (II)...

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 a preparation method of (S)-(+)-3,4,8,8a-tetrahydro-8a-methyl-1,6-(2H,7H)-naphthoquinone. According to the preparation method, an L-proline derivative is used as a chiral catalyst and microwave radiation is introduced into chiral preparation of the (S)-(+)-3,4,8,8a-tetrahydro-8a-methyl-1,6-(2H,7H)-naphthoquinone for the first time through asymmetric Robinson cyclization reaction under conventional conditions or microwave irradiation conditions. Under proper power, an L-prolinamide type catalyst can keep excellent catalysis performance and the catalysis reaction time isshortened; compared with room-temperature stirring conditions, the synthesis efficiency is greatly improved. The molecular collision is aggravated through the microwave radiation and an intermediatecan more easily pass through an energy barrier to form a transition state, so that the reaction time is remarkably shortened, the preparation efficiency of the (S)-(+)-3,4,8,8a-tetrahydro-8a-methyl-1,6-(2H,7H)-naphthoquinone is greatly improved and the synthesis period is shortened. The method is low in cost, simple and rapid, high in yield and good in stereoselectivity.

Description

technical field [0001] The invention relates to a preparation method of (S)-(+)-3,4,8,8a-tetrahydro-8a-methyl-1,6-(2H,7H)-naphthoquinone, which belongs to the asymmetric organic small molecule field of catalytic technology. Background technique [0002] (S)-(+)-3,4,8,8a-tetrahydro-8a-methyl-1,6-(2H,7H)-naphthoquinone (S)-(+)-3,4,8, 8a-tetrahydro-8a-methyl-1,6-(2H,7H)-naphthoquinone is an important starting material in the total synthesis of more than 50 natural products with antitumor, antibacterial, antiviral, Biological activities such as immune regulation and ion channel regulation are in great demand in the laboratory (kilogram level). (S)-(+)-3,4,8,8a-tetrahydro-8a-methyl-1,6-(2H,7H)-naphthoquinone is usually produced by triketone compound under the action of chiral catalyst without The symmetric Robinson cyclization reaction is prepared, and the structure of the chiral catalyst has an important influence on the effect of the asymmetric Robinson cyclization reaction....

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): C07C46/00C07C50/10C07C45/68C07C49/477
CPCC07B2200/07C07C45/68C07C46/00C07C2602/28C07C50/10C07C49/477
Inventor 潘里丁晓琴丁俊杰李大禹
Owner 中国人民解放军军事科学院防化研究院
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