Method for preparing 6-methoxy-2-acetonaphthalene

A methoxy and acetyl technology, applied in the field of medicine and chemical industry, to achieve the effect of reasonable reaction steps, less environmental pollution and high quality

Active Publication Date: 2011-06-22
江苏八巨药业有限公司
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0002]6-Methoxy-2-acetylnaphthalene is an important intermediate of the analgesic and anti-inflammatory drug Naproxen, and its traditional synthesis method is based on β- Naphthol is raw material, and Lewis acid is catalyst, is solvent with nitrobenzene or ethylene dichloride, introduces acyl group through acylation reaction with acetyl chloride, but there are more isomer products in the product prepared by this method, Thereby affecting the yield of final product 6-methoxy-2-acetylnaphthalene, in order to make acyl substitute on 2 positions, reduce the generation of other isomers, improve the yield of final product 6-methoxyl-2-acetylnaphthalene yield
Although the nitrobenzene used in this method is mainly used as a solvent and partly acts as an isomer transposition accelerator, so that the reaction steps are less, the operation is simple, the corrosion to equipment is lower, and the cost is less, but due to the nitrobenzene The role of benzene isomer transposition promotion is very small, generally it is not used as isomer transposition accelerator, but only as a solvent for the reaction. If nitrobenzene is used as isomer transposition accelerator, the amount added is too small, resulting in The yield and the purity of the final product 6-methoxy-2-acetylnaphthalene are relatively low, the yield is only about 60%, and the purity is only about 95%; Toxic will cause pollution to the environment and poison to the operator's body

Method used

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  • Method for preparing 6-methoxy-2-acetonaphthalene
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  • Method for preparing 6-methoxy-2-acetonaphthalene

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] Add 300ml of 1,2-dichloroethane, 80g of β-naphthyl methyl ether, and 9ml of nitroethane into a 500ml three-neck flask equipped with a stirrer, a thermometer, and a reflux cooler. After stirring and dissolving, cool down to 5°C~ 8°C, put in 84g of aluminum trichloride, and after dissolving, add 44g of acetyl chloride dropwise at a temperature of 10°C to 14°C. Incubate for 20 hours under the condition of 36-38° C., the product is 92.5% and the isomer is 0.8%.

[0030]Pour the above reaction liquid into crushed ice water for ice thawing, control the temperature of the reaction liquid before ice thawing to be 36-38°C, let it stand for stratification, wash the water layer with 1,2-dichloroethane once, and put the washed The organic layer was incorporated into the original organic layer, and the organic layer was distilled under normal pressure to remove the solvent 1,2-dichloroethane. After precipitating, distillation is carried out under the condition that the vacuum degre...

Embodiment 2

[0032] The reaction device is the same as in Example 1, and will not be repeated; add 450ml of 1,1-dichloroethane, 80g of β-naphthyl methyl ether, and 11ml of nitromethane, stir and dissolve, cool to 8°C to 10°C, and put in trichloride After dissolving 90g of iron, add 60g of acetyl chloride dropwise at a temperature of 15°C to 20°C. After the dropwise addition, the temperature rises slowly for 4 to 5 hours until the temperature reaches 45°C. After incubation for 18 hours, the product was sampled and detected to be 90.5%, and the isomer was 1.2%.

[0033] Pour the above reaction liquid into crushed ice water for ice thawing, control the temperature of the reaction liquid before ice thawing at 45-48°C, let it stand for stratification, wash the water layer with 1,1-dichloroethane once, and put the washed The organic layer was incorporated into the original organic layer, and the organic layer was distilled under normal pressure to remove the solvent 1,1-dichloroethane. After pr...

Embodiment 3

[0035] The reaction device is the same as in Example 1, and will not be repeated; add 300ml of 1,2-dibromoethane, 80g of β-naphthyl methyl ether, and 9ml of 1-nitropropane, stir and dissolve, cool to 3°C to 5°C, and put in chlorine After dissolving 92g of zinc chloride, add 56g of acetyl chloride dropwise at a temperature of 5°C to 10°C. After the dropwise addition, the temperature rises slowly for 3 to 4 hours until the temperature reaches 20°C. After 30 hours of incubation at high temperature, 85.3% of the product and 4.6% of isomers were detected by sampling.

[0036] Pour the above reaction liquid into crushed ice water for ice thawing, control the temperature of the reaction liquid before ice thawing at 20-25°C, let it stand for stratification, wash the water layer with 1,2-dibromoethane once, and put the washed The organic layer was incorporated into the original organic layer, and the organic layer was distilled under normal pressure to remove the solvent 1,2-dibromoeth...

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Abstract

The present invention provides a method used for preparing 6-methoxy-2-acetyl naphthalene, and belongs to the field of medicine and chemical industry. The method solves the problems of low yield, high costs, poor safety performance, and so on in the synthetic method of the 6-methoxy-2-acetyl naphthalene. The method comprises the following step: a, acylation: beta-naphthyl methyl ether and acetyl chloride are used as raw materials; Louis acid is used as a catalyst; nitro-paraffin is used as a isomer transposition promoter so as to transfer the acyl in the fifth position into the second position; thus the semi-finished product of the 6-methoxy-2-acetyl naphthalene can be prepared; b, post treatment: the crude product of the 6-methoxy-2-acetyl naphthalene is crystallized again to prepare thefinished product of the 6-methoxy-2-acetyl naphthalene. In the method, the nitro-paraffin is used as the isomer transposition promoter, and has high conversion rate. In addition, the reaction steps are reasonable and simple; the required equipment has low requirements but high security; and the method has less environmental pollution, and is suitable for the industrial production with various scales.

Description

technical field [0001] The invention relates to a method for producing a pharmaceutical intermediate, in particular to a method for producing a pharmaceutical naproxen intermediate 6-methoxy-2-acetylnaphthalene; it belongs to the technical fields of medicine and chemical industry. Background technique [0002] 6-methoxy-2-acetylnaphthalene is an important intermediate of the analgesic and anti-inflammatory drug naproxen (Naproxen). Ethylene dichloride is a solvent, and the acyl group is introduced through acylation reaction with acetyl chloride, but there are more isomer products in the product prepared by this method, which affects the final product 6-methoxyl-2-acetylnaphthalene The yield, in order to make the acyl group substitute on the 2 position, reduce the generation of other isomers, improve the yield of the final product 6-methoxy-2-acetylnaphthalene. The prior art mainly adopts two more practical synthetic methods. [0003] Method 1: first protect the 2-position...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C49/84C07C45/46
Inventor 徐斌孙守湘王玉刚华俊李观江成继志吴六君
Owner 江苏八巨药业有限公司
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