4-Methylbenzaldehyde → Lithium Hexamethyldisilazide

HRID 484050Notes

Reaction equation

HRID 484050 reaction equation
[Li:1]CCCC.[CH3:6][Si:7]([NH:10][Si:11]([CH3:14])([CH3:13])[CH3:12])([CH3:9])[CH3:8].C1(C)C=CC(C=O)=CC=1.C([Mg]Cl)C=C.[NH4+].[Cl-]>C1COCC1.O.CCO>[CH3:6][Si:7]([N-:10][Si:11]([CH3:14])([CH3:13])[CH3:12])([CH3:9])[CH3:8].[Li+:1]

Participants

9

Reactant 5

HCID 77254-MethylbenzaldehydeHCID 13838HexamethyldisilazaneHCID 25517Ammonium ChlorideHCID 178418339ButyllithiumHCID 178418473HCID 178418473, compound

Product 1

HCID 2733832Lithium Hexamethyldisilazide

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
10 °C

Procedure

A solution of lithium bistrimethylsilylamide was prepared by adding 208 ml of 2.5M n-BuLi to a solution of bistrimethylsilylamine (110 ml, 0.52 mol) in THF (140 ml) at 0° C. After stirring for 15 min, this solution was added via a cannula to a solution of p-tolualdehyde (59 ml, 0.5 mol) in THF (100 ml), while keeping the temperature between -40° and -50° C. The reaction mixture was then allowed to warm up to 10° C. over 30 min. A 2M solution of allyl magnesium chloride (260 ml) in THF was added, keeping the temperature of the reaction between 10° and 15° C. After stirring for 30 min the reaction was poured into a solution prepared by dissolving NH4Cl (150 gm) in H2O (1 liter). The layers were separated and the aqueous layer was extracted with Et2O-hexane. The organic layer was washed with brine, dried over Na2SO4 and evaporated to dryness. The residual oil was added to a solution of (1R)-(-)-10-camphorsulfonic acid (62.5 gm) in EtOAc (1 liter) with cooling. On standing overnight at room temperature, crystals were formed and these were filtered off and washed with EtOAc. The solid was stirred with refluxing EtOAc (300 ml), filtered and washed again with EtOAc. The pure product so formed weighed 60.7 gm (59%). [α]D -27.16 (c=0.5, EtOH).

Workup

  1. customthe temperature between -40° and -50° C
  2. customthe temperature of the reaction between 10° and 15° C
  3. stirringAfter stirring for 30 min the reaction
  4. additionwas poured into a solution
  5. customprepared
  6. customThe layers were separated
  7. extractionthe aqueous layer was extracted with Et2O-hexane
  8. washThe organic layer was washed with brine
  9. dry with materialdried over Na2SO4
  10. customevaporated to dryness
  11. additionThe residual oil was added to a solution of (1R)-(-)-10-camphorsulfonic acid (62.5 gm) in EtOAc (1 liter)
  12. temperaturewith cooling
  13. waitOn standing overnight at room temperature
  14. customcrystals were formed
  15. filtrationthese were filtered off
  16. washwashed with EtOAc
  17. stirringThe solid was stirred with refluxing EtOAc (300 ml)
  18. filtrationfiltered
  19. washwashed again with EtOAc
  20. customThe pure product so formed

Sources & evidence

ORD record
ord-f8714494f9814ab98a5976b60f7f4d84
Source dataset
uspto-grants-1993_07
Patent number
US05229381

Reaction notes

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