Sodium Hydroxide → Ammonia

HRID 1866530Notes

Reaction equation

HRID 1866530 reaction equation
[CH3:1][S:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]#[N:11])=[CH:5][CH:4]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].[OH-].[Na+]>O1CCCC1>[NH3:11].[CH3:1][S:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH2:10][NH2:11])=[CH:5][CH:4]=1

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 27600872-(4-(Methylthio)phenyl)acetonitrileHCID 21226445Aluminium lithium hydride2×

Product 2

HCID 222AmmoniaHCID 10535094Benzeneethanamine, 4-(methylthio)-

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 4-(methylthio)phenylacetonitrile (828 mg, 5.08 mmol) in tetrahydrofuran (10 mL) was added dropwise to lithium aluminium hydride (1M in tetrahydrofuran, 5.6 mL, 5.6 mmol) and the mixture was stirred for 1 hour at 0° C. Further lithium aluminium hydride (1M in tetrahydrofuran, 5.6 mL, 5.6 mmol) was added and the mixture was stirred at room temperature for 18 hours then heated under reflux for 1 hour. The reaction mixture was cooled to 0° C., 1M sodium hydroxide solution (3 mL) was added dropwise, and stirring continued for a further hour. The mixture was then filtered through Celite®, washing through with ethyl acetate, and the filtrate was washed with 1M sodium hydroxide solution. The organic solution was then loaded onto an Isolute® SCX cartridge, washed with methanol and eluted with 1M ammonia in methanol. The relevant fractions were concentrated in vacuo and the residue was purified by column chromatography on silica gel, eluting with dichloromethane:methanol:0.88 ammonia, 100:0:0 to 95:5:0.5, to afford the title compound as a yellow oil in 18% yield, 154 mg. 1H NMR (400 MHz, CDCl3) δ: 7.20 (2H, m), 7.14 (2H, m), 2.84 (2H, m), 2.71 (2H, m), 2.43 (3H, s) ppm; LRMS APCI m/z 168 [M+H]+

Workup

  1. stirringthe mixture was stirred at room temperature for 18 hours
  2. temperaturethen heated
  3. temperatureunder reflux for 1 hour
  4. temperatureThe reaction mixture was cooled to 0° C.
  5. stirringstirring
  6. waitcontinued for a further hour
  7. filtrationThe mixture was then filtered through Celite®
  8. washwashing through with ethyl acetate
  9. washthe filtrate was washed with 1M sodium hydroxide solution
  10. washwashed with methanol
  11. washeluted with 1M ammonia in methanol
  12. concentrationThe relevant fractions were concentrated in vacuo
  13. customthe residue was purified by column chromatography on silica gel
  14. washeluting with dichloromethane

Sources & evidence

ORD record
ord-f3952c9edacc4abda39ea31c3dfd5ff0
Source dataset
uspto-grants-2009_12
Patent number
US07629358B2

Reaction notes

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