Toluene → Non-2-yn-1-ol

HRID 398217Notes

Reaction equation

HRID 398217 reaction equation
[Li][CH2:2][CH2:3][CH2:4][CH3:5].[C:6]1(C)C=[CH:10][CH:9]=[CH:8][CH:7]=1.C#CCCCCCC.CN(P(N(C)C)(N(C)C)=[O:25])C>C1COCC1>[CH2:2]([OH:25])[C:3]#[C:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10]

Participants

6

Reactant 4

HCID 1140TolueneHCID 123701-OctyneHCID 12679HexamethylphosphoramideHCID 178418339Butyllithium

Product 1

HCID 80017Non-2-yn-1-olYield 55%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

In a 250-mL flask equipped with a stir bar, I-Pr2NH (7.34 g, 72.5 mmol) and THF (20 mL) were stirred under argon and cooled to 0° C. A 2.5-M solution of n-BuLi in toluene (29.0 mL, 72.5 mmol) was added slowly to the stirring solution. The reaction was stirred for 30 min at 0° C. and then cooled to −78° C. in a dry ice/acetone bath. Then 1-octyne was added slowly via syringe to the reaction and a white precipitate formed. To dissolve the precipitate, HMPA (23.6 g, 132 mmol) was added in one portion. The cloudy solution was stirred under argon at −78° C. for 30 minutes before warming to 0° C. when the precipitate dissolved. A solution of paraformaldehyde (CH2O)n (5.94 g, 198 mmol) in THF (60 mL) was stirred under argon at −78° C. The alkynyllitheate was then added via cannula with positive argon pressure to the (CH2O)n solution. The reaction was then allowed to warm slowly to room temperature. The reaction was quenched with water and extracted with Et2O. The organic layers were combined, washed with water and brine, dried with MgSO4, and concentrated. This produced 24.4 g of orange oil. The product was purified with flash column chromatography on silica gel (10% Et2O in hexane) to give 5.07 g of amber oil (55%):

Workup

  1. customIn a 250-mL flask equipped with a stir bar
  2. temperaturecooled to −78° C. in a dry ice/acetone bath
  3. customa white precipitate formed
  4. additionwas added in one portion
  5. stirringThe cloudy solution was stirred under argon at −78° C. for 30 minutes
  6. temperaturebefore warming to 0° C. when the precipitate
  7. dissolutiondissolved
  8. temperatureto warm slowly to room temperature
  9. customThe reaction was quenched with water
  10. extractionextracted with Et2O
  11. washwashed with water and brine
  12. dry with materialdried with MgSO4
  13. concentrationconcentrated
  14. customThe product was purified with flash column chromatography on silica gel (10% Et2O in hexane)

Sources & evidence

ORD record
ord-398163d557c24a7ebf9b5443e0bfa328
Source dataset
uspto-grants-2003_08
Patent number
US06610835B1

Reaction notes

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