Background and overview[1][2]
Cyclobutyl phenyl ketone can be used in organic synthesis, such as the preparation of benzoyl para-difluoroalkylated derivatives.
Apply[1]
Cyclobutyl phenyl ketone can be used in organic synthesis, such as the preparation of benzoyl para-difluoroalkylated derivatives. Benzoyl para-difluoroalkylated derivatives usually have significant biological activity and pharmacology. Active, such as zaltoprofen, a non-steroidal anti-inflammatory drug with anti-inflammatory, analgesic and antipyretic effects, used to treat pain and musculoskeletal system diseases such as rheumatoid arthritis; ketoprofen is used for rheumatoid arthritis arthritis, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis and gout, etc.
In addition, 2-hydroxy-4-methoxybenzophenone, whose Chinese name is UV absorber UV-9, is a broad-spectrum ultraviolet absorber that is widely used in sunscreen ointments, creams, honeys, lotions, In sunscreen cosmetics such as oil, it can also be used as an anti-discoloration agent for products that change color due to photosensitivity. In the field of fluorination research, about 30% of agricultural chemicals and 20% of all drugs contain fluorine. In particular, substances containing difluoromethyl functional groups are irreplaceable in biochemistry, pharmacy, life sciences, etc. effect. Therefore, the selective synthesis of benzoyl para-difluoroalkylated derivatives is of great value. In the prior art, there are only a few literature reports on the synthesis of this related derivative with para-selectivity. There are studies using cyclobutyl phenyl ketone as raw material, and its reaction formula is as follows:
1) Add 0.0320g (0.2mmol) of cyclobutylphenylphenone, 0.0116g (0.01mmol) of palladium tetrakistriphenylphosphine, 0.0786g (0.8mmol) of potassium acetate, and triphenylphosphine in the reaction tube. 0.0157g (0.06mmol), 0.0077g (0.06mmol) silver fluoride, 0.0203g (1.00mmol) ethyl bromodifluoroacetate and 0.25mL n-hexane, filled with argon for protection, and reacted at 140°C for 20 hours;
2) TLC follows the reaction until it is completely completed;
3) The crude product obtained after the reaction is separated by column chromatography (petroleum ether: ethyl acetate = 15:1) to obtain the target product (yield 65%).
Main reference materials
[1] CN108586251 A method for preparing benzoyl para-difluoroalkylated derivatives
