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

Method for preparing chiral alpha-chloroaziridine

A technology of aziridine and chirality, which is applied in the field of preparation of chiral α-chloroaziridines, can solve the problem of high-efficiency chiral synthesis methods of α-chloroaziridines that have not been reported and are not widely used. problems such as adaptability and selectivity, to achieve the effect of mild process conditions and economical and easy-to-obtain raw materials

Active Publication Date: 2014-04-02
SHANGHAI UNIV OF ENG SCI
View PDF4 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In addition, Darzens-type reactions of compounds containing reactive dichloromethyl groups with imines ((a) Coutrot, P.; Gadi, A.E.J. Organomet. Chem. 1985, 280, C-11; (b) Giubellina, N. ; Mangelinckx, S.; K.W.; De Kimpe, N.J.Org.Chem.2006, 71, 5881.), the addition reaction of nitrates to chloroalkenes (Pellacani, L.; Persia, F.; Tardella, P.Tetrahedron Lett.1980, 21, 4967), and the addition reaction of aziridine and acid chloride (Fowler, F.W.; Hassner, A.J.Am.Chem.Soc.1968, 90, 2875) to prepare such compounds, also have certain applications, although these This method generally does not have high universality and selectivity
However, there is no report on the efficient chiral synthesis of α-chloroaziridine

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
  • Method for preparing chiral alpha-chloroaziridine
  • Method for preparing chiral alpha-chloroaziridine
  • Method for preparing chiral alpha-chloroaziridine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] At -70°C, sodium tert-butoxide (0.96 g, 10 mmol, dissolved in 1.0 ml tetrahydrofuran) was slowly added dropwise into 2 H) (1.57 g, 10 mmol), imine represented by formula (2a) (2.1 g, 10 mmol), and 15 ml of tetrahydrofuran in a reaction flask. After reacting for 1 hour, 10 ml of water was added to terminate the reaction. The reaction solution was then transferred to a separatory funnel and extracted with ethyl acetate (50ml×2). After the organic phase was dried over anhydrous sodium sulfate, the solvent was removed under reduced pressure. Flash column chromatography with ethyl acetate / petroleum ether (volume ratio 1:5) yielded 1.62 g of product 3a with a yield of 62% and a dr of 99:1.

[0025]

[0026] Characterization data of compound 3a:

[0027]

[0028] Pale yellow liquid; mp71.1-71.8℃; [α] D 25 +54.4(c0.51, CHCl 3 ); IR (film) 2917, 1450, 1285, 1078, 918, 699cm -1 ; 1 H NMR (CDCl 3 )δ7.39(ddd, J=7.3, 4.2, 1.5Hz, 5H), 4.57(d, J=5.6Hz, 1H), 3.93(d, J=5....

Embodiment 2

[0030] At a temperature of -20°C, sodium tert-butoxide (1.92 g, 20 mmol, dissolved in 1.0 ml of N, N-dimethylformamide) was slowly added dropwise into a solution containing trimethyl(dichloromethyl)silane (TMSCCl 2 H) (3.14 g, 20 mmol), imine represented by formula (2b) (2.23 g, 10 mmol), and 15 ml of N,N-dimethylformamide in a reaction flask. After reacting for 3 hours, 10 ml of water was added to terminate the reaction. The reaction solution was then transferred to a separatory funnel and extracted with ethyl acetate (50ml×2). After the organic phase was dried over anhydrous sodium sulfate, the solvent was removed under reduced pressure. Flash column chromatography with ethyl acetate / petroleum ether (volume ratio 1:4) yielded 2.30 g of product 3b with a yield of 85% and a dr of 98:2.

[0031]

[0032] Characterization data of compound 3b:

[0033]

[0034] Pale yellow liquid; [α] D 25 +69.6 (c0.59, CHCl 3 ); IR (film) 2924, 1459, 1290, 1086, 927, 707cm -1 ; 1 H...

Embodiment 3

[0036]At a temperature of 0°C, potassium tert-butoxide (2.8 g, 25 mmol, dissolved in 2.0 ml dimethyl sulfoxide) was slowly added dropwise into 2 H) (3.92 g, 25 mmol), imine represented by formula (2c) (2.23 g, 10 mmol), and 15 ml of dimethyl sulfoxide in a reaction flask. After reacting for 3 hours, 10 ml of water was added to terminate the reaction. The reaction solution was then transferred to a separatory funnel and extracted with ethyl acetate (50ml×2). After the organic phase was dried over anhydrous sodium sulfate, the solvent was removed under reduced pressure. Flash column chromatography with ethyl acetate / petroleum ether (1:4) gave 2.44 g of product 3b with a yield of 90% and a dr of 99:1.

[0037]

[0038] Characterization data of compound 3c:

[0039]

[0040] Colorless liquid; [α] D 25 +155.9 (c0.95, CHCl 3 ); IR (film) 2923, 1477, 1293, 1082, 948, 810, 698cm -1 ; 1 H NMR (CDCl 3 )δ7.29-7.15 (m, 4H), 4.55 (d, J = 5.6Hz, 1H), 3.90 (d, J = 5.6Hz, 1H), ...

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 method for preparing chiral alpha-chloroaziridine. In an organic solvent, the chiral alpha-chloroaziridine is obtained by enabling chiral (Rs)-N-(tertiary butyl sulfonyl) imide, trimethyl (methyl dichloride) silane and alkali to react for 0.5-10h at the temperature of -80 DEG C-30 DEG C. Compared with the prior art, the chiral alpha-chloroaziridine prepared by the method provided by the invention is a potential bioactive molecular synthetic building block and can be used an important intermediate to synthesize a chiral nitrogen-containing compound, such as aziridine. According to the method for preparing the chiral alpha-chloroaziridine, provided by the invention, raw materials used for preparation are economic and easy to obtain, the preparation process conditions are mild, the method is efficient, and the optical purity of the alpha-chloroaziridine prepared by the method is high. The chiral alpha-chloroaziridine prepared by the method provided by the invention is expected to be applied to the fields of asymmetric synthesis and research and development of medicines.

Description

technical field [0001] The invention relates to a method for preparing aziridine, in particular to a method for preparing chiral α-chloroaziridine. Background technique [0002] Aziridines are an important class of organic compounds. Due to the tension of the three-membered ring, aziridines are prone to selective ring-opening reactions, and thus are often used to synthesize various nitrogen-containing compounds. α-Chloroaziridines are an important class of C-heteroaziridines (Singh, G.S.; D'hooghe, M.; De Kimpe, N. Chem. Rev., 2007, 107, 2080), It can be converted into other nitrogen-containing compounds by ring-opening reaction, and can also be converted into other important aziridine derivatives by substitution reaction ((a) Deyrup, J.A.; Greenwald, R.B.J.Am.Chem.Soc.1965, 87, 4538; (b) Hassner, A.; Burke, S.S.; Cheng-fan I, J.J. Am. Chem. Soc. 1975, 97, 4692). [0003] The method for preparing α-chloroaziridine compounds is reported to be prepared by the reaction of chl...

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): C07D203/24C07D203/02
CPCC07D203/02C07D203/24C07D401/04C07D405/04
Inventor 李亚李德升
Owner SHANGHAI UNIV OF ENG SCI
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