2,7-Dihydroxy-9-fluorenone

Background technology

2, 7-dihydroxy-9-fluorenone is an important organic synthesis material, which can be used to prepare fluorescent silicone polymeric materials. It can also be used to prepare fluorenyl polyether sulfone ketone thermoplastic resin. In addition, it can be used as a key intermediate for the synthesis of viral interferon (diethylamino-9-fluorenone) and 2-hydroxylamino-acetyl-9-fluorenone as an antispasmodic. Therefore, the synthesis of 2, 7-dihydroxy-9-fluorenone has important research value.

The synthesis of 2, 7-dihydroxy-9-fluorenone was first reported by Krishna in 1967 (Journal of Medicinal Chemistry,1967,10:99-101). Using fluorene as raw material, 2, 7-dihydroxy-9-fluorenone was obtained through sulfonation, oxidation, alkali melting and closed-loop reaction. This method is easy to obtain raw materials and low cost. However, in the preparation process, potassium permanganate is selected as the oxidant, there is a large amount of solid waste of manganese dioxide, which is difficult to deal with, and the last two steps of the reaction are high-temperature solid reaction, the operation mode and the mass transfer process in the reaction process are difficult, and the production of reaction equipment is high and it is difficult to control the degree of reaction.

In 1973, Horner et al. (Justus Liebigs Annalen der Chemie,1973,6(5):910-935.) reported that methyl 2-bromo5-methoxybenzoate and p-iodoanisole were used as raw materials in the catalysis of copper powder. 4-dimethyl ether biphenyl-2-formic acid and 4,4' -dimethyl ether dibenzoic acid. 2, 7-dihydroxy-9-fluorenone was obtained by the conversion of methoxy group to hydroxyl group by hydrobromic acid in the closed loop under the action of polyphosphate. The condition of this method is mild, but the raw material price is high, and the first step has its own coupling product, and the yield is low.

In 2008, Jeffrey et al. (Journal of Materials Chemistry,2008,18(28):3361-3365.) reported that fluorene was used as the starting material and acetic anhydride as the acylation reagent, and Fu-g acylation was carried out under the catalysis of anhydrous A1C1. The product was then subjected to Baeyer-Villiger oxidation rearrangement by m-CPBA and trifluoroacetic acid in chloroform solvent. The product was oxidized with sodium dichromate and finally hydrolyzed to 2, 7-dihydroxy-9-fluorenone. The cost of this method is high, the use of peroxide production needs to pay attention to safety, and sodium bichromate post-treatment is difficult.

At present, the production process of 2, 7-dihydroxy-9-fluorenone has the following problems: 1) Due to the shortcomings of high cost, dangerous operation, complexity and large amount of solvent, it is difficult to obtain satisfactory results in industrial preparation; 2) This route has high raw material cost, low yield and difficult product purification; 3) The last two steps of the reaction are high-temperature solid reaction, the operation mode and the mass transfer process in the reaction process are difficult, and the production requires high reaction equipment and it is difficult to control the degree of reaction.

Preparation method

1. Add 50g fluorene, 79g benzoic acid, 124g silver oxide, 2g palladium acetate and 350g toluene into the reaction vessel equipped with a thermometer, agitator and water separator, control the reaction temperature at 115℃, fractiate the water generated by the reaction while reacting, cool it down to 70℃ after 10-15 hours of reaction, filter it while it is hot, reduce the pressure and concentrate the organic layer until a large number of solids are precipitated. Add 100g methanol, heat up to 50 ℃, stir for 1h, cool down to 10℃, extract and filter to obtain 9h-fluoren-2, 7-diacyldibenzoate methyl ester, dry 105.3g at 70 ℃, yield 85.4%.

2. Add 100g9h-fluoren-2, 7-diacyldibenzoate methyl ester, 8.2g copper acetate and 650g dichloroethane into the reactor equipped with a thermometer, stirrer and constant pressure drip device. Slowly heat up to 50℃, and slowly add 118.6g70% tert-butyl peroxide. After dripping, keep warm for 10h. At the end of the reaction, the temperature was lowered to 10℃, and the wet product of 9-oxy-9h-fluoren-2, 7-diacyldibenzoate methyl ester was obtained by extraction and filtration. The wet product was washed with 20g sodium disulfite and 115g water for 1h, and the finished product of 9-oxy-9h-fluoren-2, 7-diacyldibenzoate was extracted and dried to obtain 96.8g, with a yield of 94.0%.

3. Add 700g of water, 60g of sodium carbonate, and 100G9-oxy-9h-fluoren-2, 7-diacyldibenzoate to the reaction vessel under the protection of nitrogen. Heat up 90℃ under nitrogen atmosphere and hold for 7h. At the end of the reaction, the temperature was lowered to 5℃, and 47g concentrated hydrochloric acid was slowly added to the reaction solution. After dropping, the liquid was kept warm at 5℃ for 1h, and then pumped and filtered to obtain 52g of 2, 7-dihydroxy-9-fluorenone wet product. The wet product was then washed with 52g methanol at 15-20℃ for 1h, cooled to 5℃, filtered and dried to obtain 47.1g of 2, 7-dihydroxy-9-fluorenone. The HPLC purity was 99.8% and the yield 94.2%.