反应详情

温度

5 °C

Charge 250 g of anhydrous AlCl3 (1.87 moles) to a 2 L 3-neck round bottom flask, add 300 mL fluorobenzene (307.5 g; 3.2 moles) and cool the mixture in an ice bath to 5° C. Add 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 maintain the temperature below 12° C. Warm the reaction mixture to ambient temperature gradually and agitate at r.t. for about 90 min.; check for completion by NMR. Cool the reaction mixture to 0 to 5° C., then add 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. Pour the entire mixture into a 2 L 1:1 mixture of water and ice (v/w) to precipitate out crude products, filter the white suspension and wash well with water. Add the white residue to 3 L of aqueous saturated solution (˜5%) of NaHCO3, heat the basic mixture on a steam bath for one hour and filter the batch while hot through a thin pad of celite. Cool the filtrate to r.t., add about 320 mL of concentrated HCl dropwise into the filtrate to pH 1 to crystallize out products, and agitate the white suspension in an ice bath for 30 min. Filter the batch, wash the wet cake with ice cold water and dry 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. additionAdd
2. temperaturemaintain the temperature below 12° C
3. temperatureWarm the reaction mixture to ambient temperature gradually
4. temperatureCool 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. additionPour the entire mixture
9. additioninto a 2 L 1:1 mixture of water and ice (v/w)
10. customto precipitate out crude products
11. filtrationfilter the white suspension
12. washwash well with water
13. additionAdd the white residue to 3 L of aqueous saturated solution (˜5%) of NaHCO3
14. temperatureheat the basic mixture on a steam bath for one hour
15. filtrationfilter the batch while hot through a thin pad of celite
16. temperatureCool the filtrate to r.t.
17. additionadd about 320 mL of concentrated HCl dropwise into the filtrate to pH 1
18. customto crystallize out products
19. stirringagitate the white suspension in an ice bath for 30 min
20. filtrationFilter the batch
21. washwash the wet cake with ice cold water
22. customdry in a vacuum oven at 50° C. for 16 h