The synthetic method of middle ring lactam compound

A technology for amide compounds and lactams, which is applied in the field of synthesis of mesocyclic lactams, can solve the problem that the synthesis method of mesocyclic lactams has not been reported in domestic and foreign literatures, the difficulty of drug purification is increased, the experimental operation is dangerous, etc. problems, to achieve the effect of clean and environmentally friendly reaction system, green reaction system, and novel reaction mechanism

Active Publication Date: 2020-07-03
GUANGZHOU MEDICAL UNIV
View PDF0 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there are still great challenges in the rapid and efficient synthesis of the ring lactam skeleton. Therefore, it is urgent to develop new ring expansion reactions to meet the needs of drug development.
[0004] Xin-Yuan Liu et al. (Wang, N.; Gu, Q.-S.; Li, Z.-L.; Li, Z.; Guo, Y.-L.; Guo, Z.; Liu, X. -Y.Angew.Chem.2018,130,14421-14425.) reported a method for photocatalytic synthesis of cyclic lactam compounds, but this method requires the use of transition metal photocatalyst ruthenium and 1.5 times the equivalent of chemical oxidants Hypervalent iodine, at the same time, the reaction needs to be carried out under blue light irradiation conditions in an inert atmosphere
This reaction uses a metal catalyst, which leads to the easy introduction of trace amounts of heavy metals in the drug synthesis, which greatly increases the difficulty of drug purification and brings greater trouble to the subsequent purification process; at the same time, the reaction uses an equivalent amount of hypervalent iodine as an oxidant. The waste is serious, and at the same time, it is harmful to the environment, and the experimental operation is relatively dangerous
[0005] At present, there are no domestic and foreign literature reports on the synthesis of mesocyclic lactam compounds by electrochemical methods.

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
  • The synthetic method of middle ring lactam compound
  • The synthetic method of middle ring lactam compound
  • The synthetic method of middle ring lactam compound

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0056] The invention provides a kind of synthetic method of middle lactam compound, comprises the steps:

[0057] Electrolyzing the amide compound with the structure shown in formula (I) to obtain the mesocyclic lactam compound with the structure shown in formula (II);

[0058]

[0059] in:

[0060] Ring A is: benzene ring, or 5-6 membered heteroaromatic ring;

[0061] R 1 For: H, halogen, C 1 ~C 20 Alkyl, C 6 ~C 20 Aryl, or C 1 ~C 20 alkoxy;

[0062] R 2 For: H, halogen, C 1 ~C 20 Alkyl, halogen substituted C 1 ~C 20 Alkyl, C 6 ~C 20 Aryl, C 1 ~C 20 Alkoxy, or two adjacent R 2 Together with the C atom it is attached to form C 6 ~C 10 Aryl;

[0063] R 3 For: H, halogen, C 1 ~C 20 Alkyl, C 6 ~C 20 Aryl, C 1 ~C 20 Alkoxy, or two adjacent R 3 Together with the C atom it is attached to form C 6 ~C 10 Aryl;

[0064] -X- is: O, S, or CR 3 ;

[0065] n is: 0, 1, 2 or 3;

[0066] m is: 0, 1, 2 or 3;

[0067] p and q are each independently: 0, 1, ...

Embodiment 1

[0088] Embodiment 1: Electrochemical method synthesis compound 2a

[0089]

[0090] In a 10mL single-chamber electrolytic cell, the raw material 1a (0.2mmol) and the electrolyte Bu 4 NBF 4 (0.2mmol) was added in the mixed solvent system of 5mL acetonitrile and water (volume ratio is 9:1), with graphite sheet electrode as anode, platinum sheet as cathode, under the condition of 8mA constant electric current, electrolyze, stir at room temperature 2.3 hours ( The electric quantity is 3.4 F / mol based on the material amount of the raw material 1a), and then the electrolysis is stopped, the reaction solution is transferred, concentrated, separated and purified by column chromatography to obtain 2a as a white solid, and the yield is 98%.

[0091] The characterization data of compound 2a are as follows: 1 H NMR (400MHz, CDCl 3 )δ7.74(s,1H),7.59–7.51(m,1H),7.51–7.39(m,4H),7.33–7.24(m,2H),3.43(s,2H),2.98–2.82(m, 1H),2.78–2.68(m,1H),2.60(td,J=13.1,2.7Hz,1H),2.39–2.04(m,3H);

[00...

Embodiment 2

[0095] Embodiment 2: electrochemical method synthesis compound 2b

[0096]

[0097] In a 10mL single-chamber electrolytic cell, the raw material 1b (0.2mmol) and the electrolyte Bu 4 NBF 4 (0.2mmol) was added in the mixed solvent system of 5mL acetonitrile and water (volume ratio is 9:1), with graphite sheet electrode as anode, platinum sheet as cathode, under the condition of 8mA constant electric current, electrolyze, stir at room temperature 2.3 hours ( The electric quantity is 3.4 F / mol based on the material amount of the raw material 1b), and then the electrolysis is stopped, the reaction solution is transferred, concentrated, separated and purified by column chromatography to obtain 2b as a white solid, and the yield is 88%.

[0098] The characterization data of compound 2b are as follows: 1 H NMR (400MHz, CDCl 3 )δ7.60(d, J=8.1Hz, 2H), 7.53(d, J=8.1Hz, 2H), 7.51–7.42(m, 2H), 7.32(d, J=7.5Hz, 1H), 7.28( d, J=7.5Hz, 1H), 3.43(s, 2H), 2.91–2.86(m, 1H), 2.71–2.68(m, ...

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 synthetic method of a medium-ring lactam compound. The synthetic method comprises the following step that an amide compound with the structure shown in the formula (I) is electrolyzed to obtain the medium-ring lactam compound with the structure shown in the formula (II). The lactam compound can be directly electrolyzed through an electrochemical method, so that the medium-ring lactam compound can be obtained. Application of a transition metal catalyst and a stoichiometric oxidizing agent is avoided, generation of chemical waste is avoided, and the atom economy is facilitated. The method is simple to operate, the product purity is high, purification is easy, the efficiency and yield are high, and the production cost is low; besides, reaction conditions are mild, inert gas protection is not needed, a reaction system is greener, environmentally friendly, safe, economical, capable of saving energy and protecting the environment, and more beneficial to industrial production.

Description

[0001] field of invention [0002] The invention belongs to the technical field of organic synthesis, and in particular relates to a method for synthesizing mesocyclic lactam compounds. Background technique [0003] Mesocyclic lactam compounds (7-11 membered rings) widely exist in natural products and biologically active molecules, especially in antibacterial and antitumor active molecules. However, there are still great challenges in the rapid and efficient synthesis of ring lactam skeletons. Therefore, it is urgent to develop new ring expansion reactions to meet the needs of drug development. [0004] Xin-Yuan Liu et al. (Wang, N.; Gu, Q.-S.; Li, Z.-L.; Li, Z.; Guo, Y.-L.; Guo, Z.; Liu, X. -Y.Angew.Chem.2018,130,14421-14425.) reported a method for photocatalytic synthesis of cyclic lactam compounds, but this method requires the use of transition metal photocatalyst ruthenium and 1.5 times the equivalent of chemical oxidants Hypervalent iodine, and the reaction needs to be ...

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): C07D227/087C25B3/00C25B11/12C25B9/00
CPCC25B3/00C25B9/00C25B11/057
Inventor 阮志雄徐中楠黄志星莫光权
Owner GUANGZHOU MEDICAL UNIV
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