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

Thiourea-dipicolinamide catalyst as well as preparation method and application thereof

A technology of aminobipyridine amide and pyridine amide, which is applied in the field of asymmetric catalysis, and achieves the effects of cheap chiral source, wide application range of substrate and easy access to chiral source

Inactive Publication Date: 2019-08-02
GUANGXI TEACHERS EDUCATION UNIV
View PDF1 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although several classes of efficient metal-organic bifunctional catalysts have been reported and used in the field of asymmetric synthesis, however, inexpensive amino acid-based bifunctional catalysts, especially metal-organic bifunctional catalysts with multiple hydrogen bonds, have not been reported yet.

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
  • Thiourea-dipicolinamide catalyst as well as preparation method and application thereof
  • Thiourea-dipicolinamide catalyst as well as preparation method and application thereof
  • Thiourea-dipicolinamide catalyst as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] Compound 3: Synthesis of (S)-aminobipyridinamide intermediate protected by tert-butoxycarbonyl group:

[0047]

[0048] Synthesis of compound 3a: Add dipyridylmethylamine (0.5g, 2.7mmol), 4-Dimethylaminopyridine (DMAP, 65.8mg, 0.54mmol, 0.2 equivalents) and 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDCI, 0.62g, 3.2mmol, 1.2 equivalents). After the mixture was stirred at room temperature for 12 hours, the organic phase was extracted with ethyl acetate and washed with saturated brine. The combined organic phases were dried and concentrated, separated by column chromatography, and eluted with dichloromethane / methanol 19:1 to obtain N-tert-butoxycarbonyl-(L)-alaninamide dipyridinecarboxamide intermediate 3a, Yield 82% (0.79 g, 2.2 mmol).

[0049] Synthesis of compound 3b: To N-tert-butoxycarbonyl-L-phenylalanine 1a (0.86g, 3.2mmol, 1.2 equivalents) in dichloromethane solution, dipyridylmethylamine (0.5g, 2.7mmol) was added successively , 4-dimethyla...

Embodiment 2

[0053] Compound 6: Synthesis of thiourea-dipyridinamide catalyst:

[0054]

[0055] Synthesis of compound 6a: To a solution of N-tert-butoxycarbonyl-(L)-alaninamide dipyridinecarboxamide intermediate (0.79 g, 2.2 mmol) in dichloromethane (22 mL) was added trifluoroacetic acid (2.2 mL) . The reaction mixture was de-tert-butoxycarbonylated at room temperature for 6 hours. After the completion of the reaction was tracked by thin layer chromatography (TLC), the pH value was adjusted to 10-12 with ammonia water in a zero-degree ice bath. The residue was extracted with ethyl acetate and dried over anhydrous magnesium sulfate. After the organic phase was concentrated, it was dissolved in tetrahydrofuran, 3,5-bis(trifluoromethyl)phenylisothiocyanate (0.71g, 2.6mmol) was added, concentrated after 12 hours of reaction, separated by column chromatography, dichloromethane / methanol 9:1 to obtain compound 6a. White solid, 67% yield (0.77 g, 1.5 mmol).

[0056] Synthesis of compound...

Embodiment 3

[0064] Catalytic effect experiment: the thiourea-bipyridine amide chiral catalyst 6a-6d of the present invention is applied in an asymmetric reaction, such as compound 6d in the asymmetric Michael addition reaction of nitrostyrene and diethyl malonate application, the process is as follows:

[0065] Diethyl malonate (24.0 mg, 0.15 mmol), compound 6d (5.7 mg, 0.01 mmol, 10 mol%), and ketone trifluoromethanesulfonate were sequentially added to a toluene solution of a nitrostyrene derivative (0.1 mmol) (1.8 mg, 0.005 mmol, 5 mol%). The reaction mixture was reacted at room temperature. After the completion of the reaction was traced by thin layer chromatography, it was separated by column chromatography and eluted with petroleum ether / ethyl acetate 9:1 to obtain the Michael addition product.

[0066] The reaction formula is as follows:

[0067]

[0068] The catalytic effect is shown in the table below:

[0069] Table 2

[0070]

[0071] As can be seen from the above tabl...

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 thiourea-dipicolinamide catalyst as well as a preparation method and application thereof. The catalyst has a structural formula as shown in the specification. According to the catalyst disclosed by the invention, due to a dual catalysis mode that multiple hydrogen bonds are combined with bipyridine coordination, various synthons can be activated through different metalliccenters and multiple hydrogen bond combination sites, and then the purpose of high-selectivity synthesis of a target compound can be achieved. The preparation method comprises the following steps: mixing nitrogen-protected amino acid, bipyridine methylamine, 4-dimethylamino pyridine and 1-ethyl-(3-dimethyl amino propyl) carbonyl diimine hydrochloride to carry out reactions, obtaining an intermediate, carrying out a t-butyloxycarboryl desorption protection reaction, and finally enabling the intermediate to react with 3,5-di(trifluoromethyl) phenyl isothiocyanate, thereby obtaining the thiourea-dipicolinamide catalyst. The preparation method is wide in substrate application range, cheap and easy in chiral source acquisition and few in synthesis steps. The catalyst disclosed by the inventionis used in an asymmetric Michael addition reaction, and is capable of increasing the yield of Michael addition products and improving enantioselectivity.

Description

technical field [0001] The invention relates to the technical field of asymmetric catalysis, and more specifically, the invention relates to a thiourea-bipyridinamide catalyst. Background technique [0002] The design and synthesis of chiral catalysts is one of the most challenging topics in the field of asymmetric synthesis. The development of organocatalysts with novel frameworks is of great significance to the fields of synthetic chemistry, total synthesis of natural products, and medicinal chemistry. Among them, metal-organic bifunctional catalysts are a new type of catalyst framework with multiple catalytic sites and dual catalytic modes. Because of their multi-coordination modes, high catalytic performance, and multiple catalytic active sites, they have attracted more and more researchers' attention in recent years. For example, in 2011, the Dixon research group (J.Am.Chem.Soc.2011, 133, 1710-1713) designed and synthesized a class of quinine-bistriphenylphosphine ben...

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): C07D213/40B01J31/18C07C205/53C07C201/12
CPCC07D213/40B01J31/1815C07C201/12C07B2200/07B01J2231/32B01J2531/0261C07C205/53
Inventor 肖军安
Owner GUANGXI TEACHERS EDUCATION 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