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The preparation method of 6-hydroxycoumarin

A technology for hydroxycoumarin and aminocoumarin, which is applied in the field of preparation of 6-hydroxycoumarin, can solve the problems of expensive reagents, complicated preparation process, troublesome purification, etc., and achieves reduction of production cost, simple preparation process, and source of Wide range of convenient effects

Active Publication Date: 2020-01-21
常州佳德医药科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Furthermore, in WO2004 / 94400; (2004); (A2) English, US2006 / 194871; (2006); (A1) English, Bioorganic and Medicinal Chemistry Letters; vol.17; nb.17; (2007); p.4824 In ~4828, etc., 2,5-dimethoxycinnamic acid is used as the starting material, and boron tribromide is used to demethylate in dichloromethane to prepare 6-hydroxycoumarin. In this method, The preparation process of the starting material 2,5-dimethoxycinnamic acid is also relatively complicated, and the purity of 6-hydroxycoumarin prepared by this method is not high, and the purification is also relatively troublesome
[0004] In addition, in Helvetica Chimica Acta; vol.85; nb.2; (2002); p.442~450, Heterocycles; vol.39; nb.2; (1994); p.613~622, Chemical Research in Toxicology; vol.14; nb.10; (2001); p.1386~1392, using 5-hydroxy salicylaldehyde or 5-methoxy-2 methyl salicylaldehyde and ethyl triphenylphosphine acetate, in 215°C cyclization reaction at high temperature to prepare 6-hydroxycoumarin with a yield of 70-85%. The related reagents such as triphenylphosphine ethyl acetate used in this method are difficult to source or require high temperature reaction. Or the reagents are expensive, in short, they are not suitable for industrial production

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  • The preparation method of 6-hydroxycoumarin
  • The preparation method of 6-hydroxycoumarin

Examples

Experimental program
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Effect test

Embodiment 1

[0026] In a clean 1L four-neck flask, add 100g 6-nitrocoumarin, 10.5g ferric chloride hexahydrate, 26.25g medicinal activated carbon, 500ml alcohol / N,N-dimethylformamide mixed solvent ( The ratio is 2:8v / v), stirred and mixed, heated to about 80°C, and kept for 30 minutes; then at 80°C, slowly added 81.8g of 80% hydrazine hydrate dropwise, and the dropping time was 30 minutes. At an internal temperature of 90-100°C, the stirring reaction was continued for 2 hours. After the reaction is completed, lower the temperature to 80°C, filter while it is hot, and remove the activated carbon. The filtrate is a light yellow to orange-red clear liquid; the solution is cooled to room temperature, and slowly poured into water with 3 times the amount of the solution, and a light yellow to light yellow crystal is precipitated. Solid, continue cooling at about 10°C for 2 hours, crystallization is complete; filter and dry to obtain 75.86g of 6-aminocoumarin in the form of light yellow crystalli...

Embodiment 2

[0028] In a clean 1L four-neck flask, add 100g 6-nitrocoumarin, 14.06g ferric chloride hexahydrate, 35.15g medicinal activated carbon, 700ml alcohol / N,N-dimethylformamide mixed solvent ( The ratio is 2:8v / v), stir and mix, heat to about 80°C, keep for 30 minutes; then slowly add 154.5g of 80% hydrazine hydrate dropwise at 80°C, dropwise for 30 minutes, after dropping, heat to At an internal temperature of 95-100°C, the stirring reaction was continued for 2 hours. After the reaction is completed, lower the temperature to 80°C, filter while it is hot, and remove the activated carbon. The filtrate is a light yellow to orange-red clear liquid; the solution is cooled to room temperature, and slowly poured into water with 3 times the amount of the solution, and a light yellow to light yellow crystal is precipitated. Solid, continue cooling at about 10°C for 2 hours, crystallization is complete; filter and dry to obtain 70.2g of 6-aminocoumarin in the form of light yellow crystalline...

Embodiment 3

[0029] Embodiment 3 (laboratory scale-up test):

[0030] In a clean 10L four-neck flask, add 800g 6-nitrocoumarin, 84g ferric chloride hexahydrate, 210.0g medicinal activated carbon, 4L alcohol / N,N-dimethylformamide mixed solvent ( The ratio is 2:8v / v), stirred and mixed, heated to about 80°C, and kept for 30 minutes; then at 80°C, slowly added 654.4g of 80% hydrazine hydrate dropwise, and the dropping time was 45-60 minutes, and the dropwise was completed. Heat to an internal temperature of 90-100°C, and continue to stir and react for 2 hours. After the reaction is completed, lower the temperature to 80°C, filter while it is hot, and remove the activated carbon. The filtrate is a light yellow to orange-red clear liquid; the solution is cooled to room temperature, and slowly poured into water with 3 times the amount of the solution, and a light yellow to light yellow crystal is precipitated. Solid, continue to cool at about 10°C for 2 hours, crystallization is complete; filte...

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Abstract

The invention discloses a preparation method of 6-hydroxy coumarin. The preparation method comprises the following steps of: by taking 6-nitryl coumarin as an initial raw material, preparing 6-amino coumarin through reduction; and then preparing 6-hydroxy coumarin through diazotization-hydrolysis, wherein the yield of the prepared 6-nitryl coumarin is 85.4% and the purity reaches up to 98.0%. The 6-nitryl coumarin is an important raw material for preparing benzopyran which is a critical intermediate for various anti-rheumatism drugs, blood sugar-reducing drugs and the like. According to the preparation method disclosed by the invention, the raw materials are easily available and cheap in price, the preparation process is relatively simple, and the preparation method is suitable for industrial production.

Description

technical field [0001] The invention relates to a preparation method of 6-hydroxycoumarin, in particular to a method for producing 6-hydroxycoumarin from 6-nitrocoumarin. Background technique [0002] 6-Hydroxycoumarin is a key intermediate for the preparation of benzopyran derivatives, which are widely used in pesticides, medicines, dyes and other industries, especially for the synthesis of hypoglycemic agents containing benzopyran structures. , antirheumatic and other drugs. [0003] According to foreign literature reports, the preparation of 6-hydroxycoumarin is mainly based on the synthetic route of 5-hydroxysalicylaldehyde, 5-hydroxysalicylic acid and its derivatives as starting materials. Furthermore, in WO2004 / 94400; (2004); (A2) English, US2006 / 194871; (2006); (A1) English, Bioorganic and Medicinal Chemistry Letters; vol.17; nb.17; (2007); p.4824 In ~4828, etc., 2,5-dimethoxycinnamic acid is used as the starting material, and boron tribromide is used to demethylate...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D311/14
CPCC07D311/14
Inventor 叶还青叶俊
Owner 常州佳德医药科技有限公司
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