Synthesis method of isocoumarin derivative

A technology of coumarin and compounds, applied in the field of preparation and separation and purification of isocoumarin derivatives

Inactive Publication Date: 2015-02-11
HEBEI AGRICULTURAL UNIV.
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006]The amide group structure in its structure is obtained by hydrolysis of cyano group. Conventional cyano group hydrolysis conditions generally need to be carried out under strong acid or strong alkali conditions, because isocoumarin There is a six-membered ring finger structure in the middle, the ester bond is easy to hydrolyze under the condition of strong acid or strong alkali, and the final product of the hydrolysis of the cyano group is carboxylic acid under the condition of strong acid and strong alkali, and the amide is only an intermediate product, and the conditions are not easy to control
Xiao-Yun Ma, Ying He, Yu-Lin Hu, Ming Lu.Tetrahedron Letters 53 (2012) 449–452. Introduced a method for the preparation of amides by reacting acetaldehyde oxime with cyano compounds under the catalysis of divalent copper salts, This method can convert the cyano group into an amide in a targeted manner, but when it is applied to isocoumarin, there are problems such as long reaction time, incomplete conversion, difficult separation of products and impurities, and purification.

Method used

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  • Synthesis method of isocoumarin derivative
  • Synthesis method of isocoumarin derivative
  • Synthesis method of isocoumarin derivative

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] With cuprous iodide as catalyst and DMF as solvent

[0023] Add 3.94g of 3-hexyl-4-cyano-6,7-dimethoxyisocoumarin, 1g of cuprous iodide, 15ml of DMF, and 3g of acetaldehyde oxime in sequence into a 100ml reaction vessel, and heat to reflux for 0.5h with an electric heating mantle . After the reaction system is cooled, filter with suction, add 30ml of water to the filtrate in the lower layer, a large amount of solids are precipitated, filter with suction, dissolve the filtered solid with 20ml of ethyl acetate, heat to boil, discard the black solid in the upper layer with suction, and spin evaporate the filtrate in the lower layer to dryness Then add 8ml of ethyl acetate and freeze overnight at -15°C in a freezer. After suction filtration, 2.4 g of off-white solid was obtained. The melting point is 159-162.1°C. The result of NMR characterization is: 1H NMR (600 MHz, CDCl3): δ 7.57 (s, 1H, ArH),7.29(s,2H,NH2)6.95 (s, 1H, ArH),3.99 [s, 3H, ( OCH3)], 3.97 [s, ​​3H, (OCH3...

Embodiment 2

[0025] With cuprous iodide as catalyst DMF and ethyl acetate as solvent

[0026] Add 3.94g of 3-hexyl-4-cyano-6,7-dimethoxyisocoumarin, 1g of cuprous iodide, 10ml of DMF + 5ml of ethyl acetate, 3g of acetaldehyde oxime into a 100ml reaction vessel, and use a heating mantle to Heat to reflux for 1h. After the reaction system is cooled, filter with suction, add 30ml of water to the filtrate in the lower layer, a large amount of solids are precipitated, filter with suction, heat and dissolve the filtered solid with 20ml of ethyl acetate, discard the solid in the upper layer by suction filtration while it is hot, and spin evaporate the filtrate in the lower layer to dryness Add 8ml of ethyl acetate and freeze overnight at -15°C in a freezer. After suction filtration, 2.75 g of off-white solid was obtained. The melting point is 160-162.3° C., and the retention time detected by high performance liquid chromatography is consistent with Example 1.

Embodiment 3

[0028] Cuprous bromide as catalyst

[0029] Add 3.94 g of 3-hexyl-4-cyano-6,7-dimethoxyisocoumarin, 1 g of cuprous bromide, 15 ml of DMF, and 3 g of acetaldehyde oxime in sequence into a 100 ml reaction vessel, and heat to reflux for 45 min with a heating mantle. After cooling the reaction system, filter with suction, add 30ml of water to the filtrate in the lower layer, a large amount of solids precipitate, filter with suction, dissolve the filtered solid with 8ml of ethyl acetate, and freeze overnight at -15°C in a freezer. After suction filtration, 3.19 g of off-white solid was obtained. The melting point is 161-163.3° C., and the high-performance liquid chromatography retention time is consistent with that of Example 1.

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Abstract

The invention discloses a synthesis method of an isocoumarin derivative. The method comprises the following steps: adding 3-hexyl-4-cyan-6,7-dimethoxy isocoumarin (A), a cuprous catalyst and acetaldoxime (B) in a reaction vessel, adding a solvent N,N-dimethyl formamide (DMF), stirring and refluxing; reacting for 1 hour, cooling, filtering reaction solution in vacuum, and adding a certain amount of water in the filtrate, filtering separated solid in vacuum, drying and low-temperature crystalizing obtained coarse product so as to obtain a target product 3-hexyl-4-acylamoni-6,7-dimethoxy isocoumarin (C). The method for translating the isocoumarin into acylamino is scientific and reasonable, the step is simple, the reaction time is short, the selectivity is good, the translation rate is high, the product is easy to purify; cuprous salt is firstly used as the catalyst, and the catalysis efficiency is high in comparison with the reported cupric, in particular, the cuprous has good catalysis effect on cyan hydrolysis with large steric hindrance.

Description

technical field [0001] The invention relates to a method for the preparation and separation and purification of isocoumarin derivatives. Background technique [0002] Compound 4-(2-aminopropionamido)-3,4,5,6,7,8,9,10-octahydro-5,6,8-trihydroxy-3-methyl extracted from Chrysanthemum chrysanthemum Isocoumarin, its structure is as follows: [0003] [0004] This compound has a certain herbicidal activity. According to the above structure, the compound 3-hexyl-4-amido-6,7-dimethoxyisocoumarin was synthesized by organic synthesis. Its structural formula is as follows: [0005] [0006] The amide group structure in its structure is obtained by hydrolysis of cyano group. Conventional cyano group hydrolysis conditions generally need to be carried out under strong acid or strong alkali conditions. Since isocoumarin has a six-membered ring finger structure, it can The ester bond is easily hydrolyzed, and the end product of the hydrolysis of the cyano group is a carboxylic aci...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D311/76
CPCC07D311/76
Inventor 董海焦张哲张金林赵斌霍静倩齐蒙贾子林
Owner HEBEI AGRICULTURAL UNIV.
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