反应 #982264

反应方程式

n-BuLi

tetrahydrofuran

NaOH

Acetonitrile

lithium acetonitrile

Isobutylene sulfide

THF

→

product 14

收率 39.0%

4-Mercapto-4-methylpentanoic acid

收率 39.0%

溶剂

Ethanol

water

water

反应条件

后处理

1. 1
   其他A 500 mL flask was equipped with a stir bar and a 150 mL addition funnel
2. 2
   其他was formed
3. 3
   workup.ADDITIONadded dropwise over approximately 30 min via the addition funnel
4. 4
   其他The cooling bath was removed
5. 5
   温度The flask was cooled in an ice/water bath as of 0.5 M HCl (38 mL)
6. 6
   workup.ADDITIONwas added drop-wise
7. 7
   洗涤the aqueous layer was washed twice with 75 mL of ethyl acetate
8. 8
   干燥dried over approximately 20 g of anhydrous sodium sulfate
9. 9
   其他transferred to a 250 mL flask
10. 10
    其他Solvent was removed by rotary evaporation under vacuum
11. 11
    其他to give crude 13
12. 12
    workup.ADDITIONwas slowly added
13. 13
    其他The flask was equipped with a reflux condenser
14. 14
    温度The reaction was refluxed overnight
15. 15
    温度cooled to room temperature
16. 16
    洗涤the mixture was washed with 2:1 (v/v) ethyl acetate
17. 17
    萃取extracted with ethyl acetate (3×75 mL)
18. 18
    干燥The organic layers were dried over anhydrous sodium sulfate
19. 19
    过滤filtered
20. 20
    其他the solvent was removed by rotary evaporation under vacuum

实验过程

A 500 mL flask was equipped with a stir bar and a 150 mL addition funnel. The system was placed under an argon atmosphere, and charged with anhydrous tetrahydrofuran (150 mL) and 2.5 M n-BuLi (75 mL, 18.7 mmol) in hexanes (18.7 mmol). The solution was cooled to −78° C. using a dry ice/acetone bath. Acetonitrile (7.3 g, 9.4 mL, 18 mmol) was added drop-wise via a syringe over approximately 5 min. The reaction was stirred for 30 min, while white lithium-acetonitrile precipitate was formed. Isobutylene sulfide (12), (15 g, 17 mmol) was dissolved in 100 mL of anhydrous THF and added dropwise over approximately 30 min via the addition funnel. The cooling bath was removed and the reaction was allowed to stir for 3 hours. The flask was cooled in an ice/water bath as of 0.5 M HCl (38 mL) was added drop-wise. The THF layer was retained and the aqueous layer was washed twice with 75 mL of ethyl acetate. The THF and ethyl acetate layers were combined, dried over approximately 20 g of anhydrous sodium sulfate and transferred to a 250 mL flask. Solvent was removed by rotary evaporation under vacuum to give crude 13. Ethanol (30 mL) was added, and the contents were stirred as a solution of NaOH (8.0 g) in deionized water (30 mL) was slowly added. The flask was equipped with a reflux condenser and placed under an argon atmosphere. The reaction was refluxed overnight and then cooled to room temperature. Deionized water (60 mL) was added and the mixture was washed with 2:1 (v/v) ethyl acetate:hexanes (2×25 mL). The aqueous layer was acidified to pH 2 with concentrated HCl, and then extracted with ethyl acetate (3×75 mL). The organic layers were dried over anhydrous sodium sulfate, filtered, and the solvent was removed by rotary evaporation under vacuum to give 10 g of product 14 (39% yield). The product was used without further purification. 1H NMR (CDCl3): δ 1.38 (6H, s), 1.87-1.93 (2H, m), 2.08 (1H, s), 2.51-2.57 (2H, m).

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