Ethylene Glycol → (4-(1,3-dioxolan-2-yl)phenyl)methanamine

HRID 877332Notes

Reaction equation

HRID 877332 reaction equation
[C:1]([C:3]1[CH:10]=[CH:9][C:6]([CH:7]=[O:8])=[CH:5][CH:4]=1)#[N:2].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[CH2:23](O)[CH2:24][OH:25].[H-].[Al+3].[Li+].[H-].[H-].[H-].C1COCC1.[OH-].[Na+].S([O-])([O-])(=O)=O.[Mg+2]>C1(C)C=CC=CC=1.C(OCC)(=O)C.O>[O:8]1[CH2:23][CH2:24][O:25][CH:7]1[C:6]1[CH:9]=[CH:10][C:3]([CH2:1][NH2:2])=[CH:4][CH:5]=1

Participants

11

Reactant 7

HCID 174Ethylene GlycolHCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 24083Sulfuric acid magnesium salt (1:1)HCID 660424-CyanobenzaldehydeHCID 521998p-Toluenesulfonic acid monohydrateHCID 21226445Aluminium lithium hydride

Product 1

HCID 10559254(4-(1,3-dioxolan-2-yl)phenyl)methanamineYield 87%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a stirred solution of 4-cyanobenzaldehyde (1.31 g, 10.0 mmol) and 4-toluenesulfonic acid hydrate (0.19 g, 1.0 mmol) in toluene (30 mL) was added ethylene glycol (2.30 mL, 41.2 mmol). The reaction mixture was heated at reflux under Dean and Stark conditions for 3 hours. The reaction mixture was diluted with ethyl acetate and washed with water, 10% aqueous potassium carbonate solution and brine. The organic phase was dried (magnesium sulfate), filtered and the solvent evaporated at reduced pressure. The residue was dissolved in anhydrous THF (10 mL) and added dropwise to an ice-cooled solution of lithium aluminium hydride in THF (2M in THF, 15.0 mL, 30.0 mmol). The reaction mixture was allowed to warm to room temperature at stirred at this temperature for 18 hours. Water (1.2 mL), 2M aqueous sodium hydroxide (1.2 mL) and water (3.6 mL) were added sequentially and the subsequent mixture stirred at room temperature for 30 minutes. Ethyl acetate and magnesium sulfate added and the mixture stirred for a further 30 minutes. The reaction mixture was filtered and the filtrate evaporated at reduced pressure to afford the title compound (1.56 g, 87%).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux under Dean and Stark conditions for 3 hours
  3. washwashed with water, 10% aqueous potassium carbonate solution and brine
  4. dry with materialThe organic phase was dried (magnesium sulfate)
  5. filtrationfiltered
  6. customthe solvent evaporated at reduced pressure
  7. dissolutionThe residue was dissolved in anhydrous THF (10 mL)
  8. additionadded dropwise to an ice-
  9. stirringthe subsequent mixture stirred at room temperature for 30 minutes
  10. stirringthe mixture stirred for a further 30 minutes
  11. filtrationThe reaction mixture was filtered
  12. customthe filtrate evaporated at reduced pressure

Sources & evidence

ORD record
ord-bbf6e10d30d746d6b0b6da1443ccbdfa
Source dataset
uspto-grants-2015_03
Patent number
US08987299B2

Reaction notes

Loading…