Preparation and application of 5-chloro-2-hydroxyacetophenone_Kain Industrial Additive

Background and overview^[1]

5-Chloro-2-hydroxyacetophenone can be nitrated to prepare 5-chloro-2-hydroxy-3-nitroacetophenone. 5-Chloro-2-hydroxy-3-nitroacetophenone is a key drug intermediate for the synthesis of pranlukast, which has potential application value in new drug research. Plunkast was pioneered by Japan’s Ono Pharmaceutical Co., Ltd. The world’s first leukotriene receptor antagonist was launched in Japan in 1995. Registered in Europe and the United States in 1996. It is mainly used clinically as an anti-asthmatic and anti-allergic drug and is an effective drug in the treatment of asthma. It was subsequently launched in Mexico in 2002 and is currently in Phase III clinical trials in the United States and the United Kingdom.

Preparation^[1]

Add 77.2g (0.6mol) p-chlorophenol and 73.4g (0.72mol) acetic anhydride into a 500mL three-necked flask, dropwise add 5g concentrated sulfuric acid into the flask, stir, react at 110°C for 1.5h, and reduce the pressure. Distill, the first fraction is glacial acetic acid, collect the fraction at 90°C to obtain 100g of p-chlorophenol acetate, with a purity of 98.2%;

Add 34.2g (0.2mol) p-chlorophenol acetate into a 500mL three-necked flask, slowly add 79.5g anhydrous aluminum trichloride (about 0.6mol) into the flask, and stir for 1 hour at 130°C. After the reaction, slowly add 200 mL of water to the flask, stir for 0.5 h, filter, heat and dissolve the filter cake with methanol, decolorize with activated carbon, and recrystallize to obtain 30.8 g of 5-chloro-2-hydroxyacetophenone with a purity of 99.68%.

Apply^[1]

5-Chloro-2-hydroxyacetophenone can be nitrated to prepare 5-chloro-2-hydroxy-3-nitroacetophenone. Add 43g (0.25mol) of 5-chloro-2-hydroxyacetophenone into a 500mL three-necked flask, slowly add 200mL of glacial acetic acid to the flask, stir and slowly dissolve, then add 24.3g of 90% nitric acid and 20mL of The mixture of glacial acetic acid was slowly added to the flask and reacted at 25°C. The dropwise addition was completed within an hour. The reaction was kept for 3 hours. Filter to obtain 49g of 5-chloro-2-hydroxy-3-nitroacetophenone. The mother liquor was recycled and used again. , purity is 99.5%.

References

[1][Chinese invention] Preparation method of CN201410677112.05-chloro-2-hydroxy-3-nitroacetophenone