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

A large sterically hindered chiral quaternary ammonium salt phase transfer catalyst derived from cinchonadine and its synthesis method

A technology of phase transfer catalyst and cinchona base, which is applied in the direction of organic chemical methods, organic compound/hydride/coordination complex catalysts, chemical instruments and methods, etc., can solve the problems of poor stability and low yield, and achieve low cost Low cost, simple preparation method, simple synthesis effect

Active Publication Date: 2022-08-09
NANJING TECH UNIV
View PDF0 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Due to the poor stability of this cinchona-modified quaternary ammonium salt under the oxidation condition of potassium permanganate, even if stoichiometric quaternary ammonium salt is used in the reaction, only moderate enantioselectivity and low yield can be achieved

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 large sterically hindered chiral quaternary ammonium salt phase transfer catalyst derived from cinchonadine and its synthesis method
  • A large sterically hindered chiral quaternary ammonium salt phase transfer catalyst derived from cinchonadine and its synthesis method
  • A large sterically hindered chiral quaternary ammonium salt phase transfer catalyst derived from cinchonadine and its synthesis method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] Preparation of catalyst C3(Ar 2 is 3,5-di-tert-butylphenyl), and its synthetic method comprises the following steps:

[0041]

[0042] Among them, Ar 2 For 3,5-di-tert-butylphenyl.

[0043] (1) Synthesis of 3,5-bis(3,5-di-tert-butylphenyl)benzaldehyde: under nitrogen protection, 3,5-dibromobenzaldehyde (1.57g, 6mmol), 3,5-dibromobenzaldehyde tert-Butylbenzeneboronic acid (12mmol) and Pd(PPh 3 ) 4 (69.3 mg, 0.06 mmol was dissolved in 12 mL of THF (oxygen was removed by bubbling). After stirring at room temperature until the solid reactants were completely dissolved, Na was added to the reaction system. 2 CO 3 (3.8 g, 36 mmol) in water (6 mL). The reaction system was heated to reflux temperature. After the reaction was completed, the mixture was filtered through celite. The filtrate was extracted three times with ethyl acetate. The organic phases were combined and dried over anhydrous sodium sulfate. After concentration under reduced pressure, it was purified...

Embodiment 2

[0050] Preparation of catalyst C4

[0051]

[0052] (1) Cinchonadine (118 mg, 0.4 mmol) was dissolved in toluene (6 mL), 3,4-difluorobenzyl bromide (160 mg, 0.52 mmol) was added, and the mixture was heated under reflux for 2 hours. After the reaction, the quaternary ammonium salt I (178mg, 89%) of N-3,4-difluorobenzyl chinatine was obtained by silica gel column chromatography;

[0053] (2) Dissolve N-3,4-difluorobenzyl quinatine quaternary ammonium salt I (178 mg, 0.356 mmol) in dichloromethane (6 mL), add 3,5-bis(3,5-di-tert-butyl) phenyl)benzyl bromide (594 mg, 1.07 mmol) and 50% KOH aqueous solution (100 mg, 1.78 mmol), the reaction was separated by column chromatography to obtain a large sterically hindered N-3,4-difluorobenzyl-O- 3,5-bis(3,5-di-tert-butylphenyl)benzyl quinate-derived quaternary ammonium salt catalyst C4 (267 mg, 75%).

Embodiment 3

[0055] Preparation of catalyst C5

[0056]

[0057] (1) Synthesis of 2-bromo-3,5-di-tert-butylbenzyl bromide: 3,5-di-tert-butyltoluene (409 mg, 2.0 mmol) was dissolved in anhydrous CH 3 In CN, FeCl was added successively at room temperature 3 (65 mg, 0.4 mmol) and NBS (374 mg, 2.1 mmol). The reaction was heated to 82°C and stirring was continued for 4 hours. After the reaction, the obtained solution was cooled to room temperature, and the solvent was removed by rotary evaporation.

[0058] The crude product was purified by silica gel column chromatography using petroleum ether as eluent to obtain 2-bromo-3,5-di-tert-butyltoluene in 89% yield. 2-Bromo-3,5-di-tert-butyltoluene (468 mg, 2.0 mmol) was dissolved in cyclohexane, NBS (324 mg, 2.06 mmol) and BPO (13 mg, 0.066 mmol) were added in sequence at room temperature, and heated to 80 °C, refluxed for 4 hours. After the reaction was completed, the solvent was removed by rotary evaporation. The crude product was purifie...

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 large sterically hindered chiral quaternary ammonium salt phase transfer catalyst derived from cinchona alkaloid, a synthesis method and application thereof, and belongs to the technical field of asymmetric catalysis. In the present invention, cinchonadine is dissolved in an organic solvent, benzyl bromide is added, and the N-benzyl chinchnaline quaternary ammonium salt catalyst is obtained by reaction; the product is dissolved in an organic solvent, and a corresponding large sterically hindered benzyl group is added. Bromine and an inorganic base solution are reacted and purified to obtain a large sterically hindered chiral quaternary ammonium salt catalyst derived from cinchona base. The application of this type of large sterically hindered catalyst to the reaction of potassium permanganate oxidation of olefins to synthesize chiral α-hydroxy-β-keto ester can significantly improve the enantioselectivity of the product α-hydroxy-β-keto ester.

Description

technical field [0001] The invention relates to the field of asymmetric catalysis, in particular to a large sterically hindered chiral quaternary ammonium salt phase transfer catalyst derived from cinchona, a synthesis method and application thereof. Background technique [0002] As Bronsted bases, cinchona alkaloids are excellent organic catalysts in the field of synthetic chemistry, and their derivatives have attracted extensive attention. Cinchonine (CN), Cinchonidine (CD), Quinine (QN) and Quinidine (QD) can be extracted from the bark of Cinchona. These four structures are the most commonly used structural units in cinchona alkaloid phase transfer catalysts, and a large number of phase transfer catalysts can be prepared by modifying them. [0003] Since Dolling et al. first used cinchonaine quaternary ammonium salts as chiral phase transfer catalysts to catalyze the asymmetric alkylation of cyclic indanone substrates in 1984, the reaction efficiency has been significant...

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): C07D453/04B01J31/02C07C67/313C07C69/716C07C201/12C07C205/43C07C69/738
CPCC07D453/04B01J31/0239B01J31/0244B01J31/0271C07C67/313C07C201/12C07B2200/07C07C69/716C07C205/43C07C69/738Y02P20/584
Inventor 王超李娟李双庆
Owner NANJING TECH 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