Ethylene Glycol → p-Anisidine, N-cyclohexyl-

HRID 1883385Notes

Reaction equation

HRID 1883385 reaction equation
[O-]P([O-])([O-])=O.[K+].[K+].[K+].[CH:9]1([NH2:15])[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1.C(O)CO.I[C:21]1[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=1.N>C(O)CCC.O.[Cu]I>[CH3:28][O:27][C:24]1[CH:25]=[CH:26][C:21]([NH:15][CH:9]2[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)=[CH:22][CH:23]=1

Participants

9

Reactant 5

HCID 174Ethylene GlycolHCID 222AmmoniaHCID 7965CyclohexylamineHCID 62657Potassium Phosphate, TribasicHCID 696764-Iodoanisole

Product 1

HCID 13071p-Anisidine, N-cyclohexyl-Yield 70%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 2631-ButanolSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

An oven-dried resealable 15 mL Schlenk tube was charged with CuI (9.5 mg, 0.0499 mmol, 5.0 mol %), K3PO4 (440 mg, 2.07 mmol), evacuated and backfilled with argon. Cyclohexylamine (144 μL, 1.26 mmol), ethylene glycol (0.11 mL, 1.97 mmol), and a solution of 4-iodoanisole (235 mg, 1.00 mmol) in 1-butanol (1.0 mL) were added under argon. The Schlenk tube was sealed with a Teflon valve and the reaction mixture was stirred magnetically at 100° C. for 14 h. The resulting thick, green-brown suspension was allowed to reach room temperature, poured into a solution of 30% aq ammonia (1 mL) in water (20 mL), and extracted with 3×15 mL of CH2Cl2. The colorless organic phase was dried (Na2SO4), concentrated, and the residue was purified by flash chromatography on silica gel (2×15 cm; hexane-ethyl acetate 5:1; 15 mL fractions). Fractions 9-17 provided 143 mg (70% yield) of the product as white crystals. 1H NMR (400 MHz, CDC3): δ 6.79−6.72 (m, 2H), 6.60−6.53 (m, 2H), 3.74 (s, 3H), 3.22 (br s, 1H), 3.16 (tt, J=10.2, 3.6 Hz, 1H), 2.10−1.98 (m, 2H), 1.80−1.69 (m, 2H), 1.68−1.58 (m, 1H), 1.40−1.04 (m, 5H). 13C NMR (100 MHz, CDCl3): δ 151.8, 141.6, 114.8, 114.7, 55.8, 52.7, 33.6, 25.9, 25.0. IR (neat, cm−1): 3388, 1509, 1239, 1038, 818. Anal. Calcd. for C13H19NO: C, 76.06; H, 9.33. Found: C, 76.00; H, 9.32.

Workup

  1. customevacuated
  2. customThe Schlenk tube was sealed with a Teflon valve
  3. customto reach room temperature
  4. extractionextracted with 3×15 mL of CH2Cl2
  5. dry with materialThe colorless organic phase was dried (Na2SO4)
  6. concentrationconcentrated
  7. customthe residue was purified by flash chromatography on silica gel (2×15 cm; hexane-ethyl acetate 5:1; 15 mL fractions)

Sources & evidence

ORD record
ord-273ab01952d140cfaedab0ec645b3506
Source dataset
uspto-grants-2004_07
Patent number
US06759554B2

Reaction notes

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