Reaction #1265376

Reaction equation

n-BuLi

tetrahydrofurane

Acetonitrile

lithium acetonitrile

NaOH

Isobutylene sulfide

THF

→

product 7

Yield 39.0%

4-Mercapto-4-methylpentanoic acid

Yield 39.0%

Solvents

Ethanol

water

water

Conditions

Workup

1. 1
   OtherA 500 mL flask was equipped with a stir bar and a 150 mL addition funnel
2. 2
   Otherwas formed
3. 3
   workup.ADDITIONadded drop wise over approximately 30 min via the addition funnel
4. 4
   OtherThe cooling bath was removed
5. 5
   TemperatureThe flask was cooled in an ice/water bath as 38 mL of 0.5 M HCl
6. 6
   workup.ADDITIONwas added drop-wise
7. 7
   Washthe aqueous layer was washed twice with 75 mL of ethyl acetate
8. 8
   Dryingdried over approximately 20 g of anhydrous sodium sulfate
9. 9
   Othertransferred to a 250 mL flask
10. 10
    OtherSolvent was removed by rotary evaporation under vacuum
11. 11
    Otherto give crude 6
12. 12
    workup.ADDITIONwas slowly added
13. 13
    OtherThe flask was equipped with a reflux condenser
14. 14
    TemperatureThe reaction was refluxed overnight
15. 15
    Temperaturethen cooled to room temperature
16. 16
    Extractionthe mixture was extracted twice with 25 mL portions of a 2:1 mixture of ethyl acetate and hexane
17. 17
    Extractionthen extracted three times with 75 mL portions of ethyl acetate
18. 18
    DryingThe organic layers were dried over anhydrous Na2SO4 and solvent
19. 19
    Otherwas removed by rotary evaporation under vacuum

Procedure

A 500 mL flask was equipped with a stir bar and a 150 mL addition funnel. The system was placed under an argon atmosphere. 150 mL of anhydrous tetrahydrofurane (THBF) and 75 mL of 2.5 M n-BuLi in hexanes (18.7 mmol) were added via a canula and the solution was cooled in a −78° C. 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 (15 g, 17 mmol) was dissolved in 100 mL of anhydrous THF and added drop wise 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 38 mL of 0.5 M HCl 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 6. Ethanol (30 mL) and a stir bar were added. The contents were stirred as a solution of 8.0 g NaOH in 30 mL deionized water was slowly added. The flask was equipped with a reflux condenser and placed under an argon atmosphere. The reaction was refluxed overnight then cooled to room temperature. Deionized water (60 mL) was added and the mixture was extracted twice with 25 mL portions of a 2:1 mixture of ethyl acetate and hexane. The aqueous layer was acidified to pH 2 with concentrated HCl then extracted three times with 75 mL portions of ethyl acetate. The organic layers were dried over anhydrous Na2SO4 and solvent was removed by rotary evaporation under vacuum to give 10 g of product 7 (39% yield). Material was used without further purification. 1H NMR (CDCl3): δ1.38 (6H, s), 1.87-1.93 (2H, m), 2.08 (1H, s), 2.51-2.57 (2H, m).

Source