Eureka AIR delivers breakthrough ideas for toughest innovation challenges, trusted by R&D personnel around the world.

Preparation method of 3-methylene isoindole-1-one derivatives

A technology of methylene isoindoles and derivatives, applied in the field of preparation of organic compounds, achieving the effects of high yield, mild reaction conditions, and easy availability of raw materials

Active Publication Date: 2017-05-24
SUZHOU UNIV
View PDF0 Cites 6 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] Research workers engaged in organic chemical industry are well aware that the price of substituted o-iodobenzamide or o-bromobenzamide is far more expensive than o-chlorobenzamide, but there is no literature report on the high yield synthesis of o-chlorobenzamide 3 -Methods of Methyleneisoindol-1-one Derivatives

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 3-methylene isoindole-1-one derivatives
  • Preparation method of 3-methylene isoindole-1-one derivatives
  • Preparation method of 3-methylene isoindole-1-one derivatives

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] The synthesis of 3-benzylidene 2-phenylisoindol-1-ketone (3a), the reaction formula is as follows:

[0037]

[0038] (1) Weigh o-chlorobenzanilide 1a (0.116g, 0.5mmol), phenylacetylene 2 (0.061g, 0.6mmol), 1,10-phylloline (0.009g, 0.05mmol) and dissolve in 2mL acetonitrile , potassium carbonate (0.138 g, 1 mmol), copper oxide (0.004 g, 0.05 mmol) were added. The mixture was heated to 90° C. under the protection of argon, and the reaction was followed by TLC until the reaction was completely completed. After the reaction, the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 4:1) to obtain compound 3a. Isolated yield was 48%.

[0039] (2) Weigh o-chlorobenzanilide 1a (0.116g, 0.5mmol), phenylacetylene 2 (0.061g, 0.6mmol), 1,10-phylloline (0.009g, 0.05mmol) and dissolve in 2mL acetonitrile , adding potassium carbonate (0.138g, 1mmol), nano copper oxide (0.004g, 0.05mmol). The mixture was heated to 90° C. under the prot...

Embodiment 2

[0063] The synthesis of 3-benzylidene-2-(o-tolyl)isoindol-1-one (3b), the reaction formula is as follows:

[0064]

[0065] Weigh o-chlorobenzoyl-o-toluidine 1b (0.123g, 0.5mmol), phenylacetylene 2 (0.061g, 0.6 mmol), and 1,10-phylloline (0.009g, 0.05mmol) were dissolved in 2mL of acetonitrile, Potassium carbonate (1.0 mmol), nano copper oxide (0.004 g, 0.05 mmol) were added. The mixture was heated to 90° C. under the protection of argon, and the reaction was followed by TLC until the reaction was completely completed. After the reaction, the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 4:1) to obtain compound 3b. The isolated yield was 86%.

[0066] NMR and high-resolution mass spectrometry are performed on the separated product 3b, as follows:

[0067] 1 H NMR (400MHz, CDCl 3 )δ: 7.95(d, J=7.5Hz, 1H), 7.85(d, J=7.8Hz, 1H), 7.67(t, J=7.4Hz, 1H), 7.55(t, J=7.4Hz, 1H) , 7.05–6.85 (m, 7H), 6.80 (d, J=7.7Hz, 1H), 2.12 (...

Embodiment 3

[0071] The synthesis of 3-benzylidene-2-(p-tolyl)isoindol-1-one (3c) has the following reaction formula:

[0072]

[0073] Weigh o-chlorobenzoyl-p-toluidine 1c (0.123g, 0.5mmol), phenylacetylene 2 (0.061g, 0.6mmol), and 1,10-phylloline (0.009g, 0.05mmol) were dissolved in 2mL of acetonitrile, Potassium carbonate (0.138g, 1mmol) and nano copper oxide (0.004g, 0.05mmol) were added. The mixture was heated to 90° C. under the protection of argon, and the reaction was followed by TLC until the reaction was completely completed. After the reaction, the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 4:1) to obtain compound 3c. The isolated yield was 87%.

[0074] NMR and high-resolution mass spectrometry are performed on the separated product 3c, as follows:

[0075] 1 H NMR (400MHz, DMSO) δ: 7.93(d, J=7.6Hz, 1H), 7.83(d, J=7.7Hz, 1H), 7.65(t, J=7.5Hz, 1H), 7.52(t, J =7.4Hz, 1H), 7.00–6.82(m, 9H), 6.80(s, 1H), 2.21(s, 3H).

...

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 3-methylene isoindole-1-one derivatives. The preparation method comprises the following steps: an N-substituted 2-chlorobenzamide derivative in formula (1), alkyne-terminated compounds in formula (2) and nitrogen-containing ligands react in an organic solvent at 80-100 DEG C in the presence of potassium carbonate and a copper salt catalyst, and the 3-methylene isoindole-1-one derivatives in formula (3) are obtained. The equation is shown in the specification, wherein R<1>, R<2>, R<3> and R<4> are hydrogen; R<5> is C1-C6 alkyl or aromatic, and aromatic is phenyl, benzyl or substituted benzyl; R<6> is phenyl, C2-C6 alkyl, acetoxy methylene or p-tolyloxy methylene. High-yield 3-methylene isoindole-1-one derivatives can be obtained with the method; reaction conditions are mild, reaction operation and a post-processing process are simple, and the method is suitable for large-scale production.

Description

technical field [0001] The invention relates to the technical field of preparation of organic compounds, in particular to a method for synthesizing 3-methyleneisoindol-1-one derivatives. Background technique [0002] Isoindol-1-one derivatives have good biological and pharmacological activities, and are important basic structural units of many natural products and pharmaceutical intermediates. 3-Methyleneisoindol-1-one derivatives have good biological activities, such as anti-ulcer, anti-inflammation, anti-hypertension, anti-leukemia and anesthesia. [0003] So far, the synthetic methods of 3-methyleneisoindol-1-one derivatives mainly contain the following types: [0004] 1. Synthesis of 3-methylene isoindol-1-one from phthalimide derivatives (Tetrahedron Lett.1969,10,1161; J.Org.Chem.1998,58,1740-1745, Tetrahedron Lett .1996,37,7707; Synlett.2004,13,2347, Tetrahedron.2006,62,706), but this type of method has a long route, and organometallic compounds such as Wittig reagen...

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
IPC IPC(8): C07D209/46
CPCC07D209/46
Inventor 曾润生张周晔邹建平
Owner SUZHOU 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
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