反应详情

温度

5 °C

Charged 260 g of anhydrous AlCl3 (1.87 moles) to a 2 L 3-neck round bottom flask, added 300 mL fluorobenzene (307.5 g; 3.2 moles) and cooled the mixture in an ice bath to 5° C. Added a hazy suspension of 100 g glutaric anhydride (0.86 mole) in 400 mL fluorobenzene (4.3 moles) through an addition funnel over a period of 45 min., and maintained the temperature below 12° C. The reaction mixture was warmed to ambient temperature gradually and agitated at r.t. for about 90 min.; checked for completion by NMR. Cooled the reaction mixture to 0 to 5° C., then added a cold aqueous solution (700 ml) of 1N HCl carefully to the mixture to destroy any unreacted AlCl3, keeping the temperature of the mixture below 20° C. during the early part of the acid addition, and below 40° C. for the rest of the time. Poured the entire mixture into a 2 L 1:1 mixture of water and ice (v/w) to precipitate out crude products, filtered the white suspension and washed well with water. Added the white residue to 3 L of aqueous saturated solution (˜5%) of NaHCO3, heated the basic mixture on a steam bath for one hour and filtered the batch while hot through a thin pad of celite. Cooled the filtrate to r.t., added about 320 mL of concentrated HCl dropwise into the filtrate to pH 1 to crystallize out products, and agitated the white suspension in an ice bath for 30 min. Filtered the batch, washed the wet cake with ice cold water and dried in a vacuum oven at 50° C. for 16 h to obtain 143.2 g of 4-(4-fluorobenzoyl)-butyric acid; m.p. 141 to 142° C., isolated yield: 79.3%.

1. additionAdded
2. temperaturemaintained the temperature below 12° C
3. temperatureThe reaction mixture was warmed to ambient temperature gradually
4. temperatureCooled the reaction mixture to 0 to 5° C.
5. customto destroy any unreacted AlCl3
6. customthe temperature of the mixture below 20° C.
7. additionduring the early part of the acid addition, and below 40° C. for the rest of the time
8. additionPoured the entire mixture
9. additioninto a 2 L 1:1 mixture of water and ice (v/w)
10. customto precipitate out crude products
11. filtrationfiltered the white suspension
12. washwashed well with water
13. additionAdded the white residue to 3 L of aqueous saturated solution (˜5%) of NaHCO3
14. temperatureheated the basic mixture on a steam bath for one hour
15. filtrationfiltered the batch while hot through a thin pad of celite
16. temperatureCooled the filtrate to r.t.
17. additionadded about 320 mL of concentrated HCl dropwise into the filtrate to pH 1
18. customto crystallize out products
19. stirringagitated the white suspension in an ice bath for 30 min
20. filtrationFiltered the batch
21. washwashed the wet cake with ice cold water
22. customdried in a vacuum oven at 50° C. for 16 h