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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
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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

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  • 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).

...

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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

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Application Information

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