Solid-phase synthesis method of coumarin and analogue thereof

A technique of solid-phase synthesis and analogues, applied in organic chemistry and other fields

Inactive Publication Date: 2013-10-23
YUNNAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] The object of the present invention is to solve the low yield in the solid phase synthesis method of existing coumarin and its analogues and to obtain a large amount of coumarin with aroma simply and efficiently in a short time The problem of the compounds of coumarin and its analogue parent structure provides a solid-phase synthesis method of coumarin and its analogue (I) with simple operation, good yield and high purity

Method used

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  • Solid-phase synthesis method of coumarin and analogue thereof
  • Solid-phase synthesis method of coumarin and analogue thereof
  • Solid-phase synthesis method of coumarin and analogue thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Example 2 Under nitrogen protection, 1% cross-linked polystyrene supported selenium bromide (II) (Br% = 0.99mmol / g) (2.5g, 2.48mmol), tetrahydrofuran (80mL) and N, N-di Methylformamide (20 mL) was placed in a reaction flask and allowed to stand at room temperature for 4 h. After the resin was swollen, sodium borohydride (0.473g, 12.5mmol) was added, stirred at 40°C for 2h, allyl bromide (1.572g, 13.0mmol) was added dropwise, and stirred at 40°C for 5h. After the reaction is completed, filter with a sand core funnel, and then use dichloromethane (5×10mL), water (3×10mL), water+tetrahydrofuran (V / V=1:1, 3×10mL), tetrahydrofuran (3×10mL) , ethanol (3×10mL), methanol (3×10mL), ether (3×10mL), dichloromethane (10mL), acetone (3×10mL) to wash the resin, and dry to obtain polystyrene-loaded allyl selenide (III) (2.35 g, 98.0%), IR is consistent with Example 1.

[0039] Example 3 Under nitrogen protection, 1% cross-linked polystyrene supported selenium bromide (II) (Br% = 0.9...

Embodiment 3

[0041] Example 5 Under nitrogen protection, 1% cross-linked polystyrene supported selenium bromide (II) (Br% = 0.99mmol / g) (2.5g, 2.48mmol), tetrahydrofuran (24mL) and absolute ethanol (6mL ) in a reaction flask and let it stand at room temperature for 4h. After the resin was swollen, sodium borohydride (189.2mg, 5.0mmol) was added, and the reaction was stirred at 10°C for 48h. Allyl bromide (0.665g, 5.5mmol) was added dropwise, and the reaction was continued at 20°C for 24h. After the reaction is complete, filter with a sand core funnel, and then use dichloromethane (3×10mL), water (3×10mL), water+tetrahydrofuran (V / V=1:1, 3×10mL), tetrahydrofuran (3×10mL) , ethanol (3×10mL), methanol (3×10mL), ether (3×10mL), dichloromethane (10mL), acetone (3×10mL) to wash the resin, and dry to obtain polystyrene-loaded allyl selenide (III) (2.2 g, 92.0%), IR is consistent with Example 1.

Embodiment 4

[0042] Example 6 Polystyrene-supported allyl selenide (III) (1.0 g, 0.97 mmol) and anhydrous dichloromethane (15 mL) were placed in a reaction flask, and allowed to stand at room temperature for 4 h. After the resin was swollen, N-chlorosuccinimide (0.668 g, 5.0 mmol) was added at 0° C., stirred for 5 h at 0° C., and then stirred for 24 h at room temperature. After the reaction was completed, filter with a sand core funnel, and wash the resin with dry dichloromethane (4×10 mL) to obtain polystyrene-loaded selenosuccinimide (IV). Immediately continue to soak the obtained resin (IV) with dry dichloromethane (15mL), cool to -78°C, add trimethylsilyl trifluoromethanesulfonate (0.022g, 0.10mmol), The reaction was stirred for 0.5h. 3-Phenylacrylate-4'-methylphenyl ester (V) (1.19g, 5.0mmol) was added, and the reaction mixture was kept at -20°C for 8h after continuing stirring at -78°C for 2h. After the reaction was complete, a saturated solution of sodium bicarbonate (5 mL) was ad...

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Abstract

The invention relates to a solid-phase synthesis method of coumarin and an analogue (I) thereof and belongs to the field of organic chemistry. The method comprises the following steps: 1) taking 1% of cross-linked polystyrene resin as a carrier to prepare a polystyrene-supported seleno-succimide reagent (III); 2) using the III to induce phenyl acrylate (V) to perform intramolecular cyclization under the catalysis of trimethylsilyl trifluoromethanesulfonate so as to form 3-polystyrene-supported seleno-3,4-dihydro-benzopyran-2-ketone (VI); and 3) performing oxidation elimination on the VI via an oxidant so as to directly get the coumarin (I) without further separation. When the phenyl acrylate (V) is replaced by N-phenyl acrylamide, the analogue of the coumarin, namely a 2-quinolone compound, can be prepared through the same steps. The solid-phase synthesis method disclosed by the invention has the advantages of easily available raw materials, good product yield, high purity, simplicity and convenience in operation, simple post-treatment and great industrial application prospects.

Description

technical field [0001] The invention belongs to the field of organic chemistry, and relates to a solid phase synthesis method of coumarin and its analog (I). [0002] [0003] where R 1 = H, C 1-2 Alkyl, substituted phenyl; R 2 =H, alkyl, alkoxy; Z is 0 (oxygen) or N (nitrogen)-R, when Z is N-R, R=C 1-2 alkyl. Background technique [0004] Coumarin and its analogs (I) are natural products that widely exist in nature and have various biological activities. Their parent structures are also present in many drug molecules. In the process of research and development of new drugs, the solid-phase synthesis technology in combinatorial chemistry provides a simple and quick tool for the large-scale synthesis of different derivatives of the same parent structure and high-throughput activity screening. In solid phase synthesis, selenium is an ideal linker and polymer reagent. Due to the weak carbon-selenium bond energy, organoselenium compounds can be used as important organ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D215/227C07D311/18
Inventor 汤峨李文
Owner YUNNAN UNIV
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