反応 #2501392

反応方程式

2,2,6,6-tetramethylpiperidine

hydrochloric acid

1-bromo-3,4-difluorobenzene

DMF

n-butyllithium

→

2-bromo-5,6-difluorobenzaldehyde

収率 56.2%

溶媒

tetrahydrofuran

water

反応条件

後処理

1. 1
   温度This temperature is maintained for 4 hours
2. 2
   抽出extracted with tert-butyl methyl ether
3. 3
   洗浄The combined organic extracts are washed with saturated sodium chloride solution
4. 4
   その他dried
5. 5
   その他The solvent is removed under reduced pressure
6. 6
   その他the raw product is purified by chromatography over silica gel (eluent: dichloromethane/n-heptane 1:1) and recrystallization from n-heptane

実験手順

A solution of 152 mmol of 2,2,6,6-tetramethylpiperidine and 152 mmol of n-butyllithium (1.6 M solution in n-hexane) in 280 ml of dry tetrahydrofuran is admixed with 145 mmol of 1-bromo-3,4-difluorobenzene at −75° C. This temperature is maintained for 4 hours, and then 174 mmol of DMF are added dropwise. The reaction mixture is then slowly thawed, hydrolyzed with water at −20° C., acidified using hydrochloric acid and extracted with tert-butyl methyl ether. The combined organic extracts are washed with saturated sodium chloride solution and dried using sodium sulfate. The solvent is removed under reduced pressure, and the raw product is purified by chromatography over silica gel (eluent: dichloromethane/n-heptane 1:1) and recrystallization from n-heptane, yielding 18 g (56%) of 2-bromo-5,6-difluorobenzaldehyde in the form of slightly yellow crystals.—M.p.: 40-43.5° C.—1H-NMR (400 MHz, CDCl3/TMS): δ=10.31 (dd, 4J(HF)=2 Hz, 5J(HF)=1.5 Hz, 1 H, CHO), 7.45 (ddd, 3J(HH)=9 Hz, 4J(HF)=4 Hz, 5J(HF)=2 Hz, 1 H, Har), 7.28 (ddd, 3J(HH)=9 Hz, 3J(HF)=9 Hz, 4J(HF)=8 Hz, 1 H, Har).—19F-NMR (376.5 MHz, 1H broad-band decoupled, CDCl3/CFCl3): δ=−136.4 (d, 3J=19.2 Hz), −139.2 (d, 3J=19.2 Hz).

出典