4-Bromoanisole → 1,1,2-Tris(4-methoxyphenyl)ethan-1-ol

HRID 2050950Notes

Reaction equation

HRID 2050950 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=1.[C:10]1([C:18]([CH2:20][C:21]2[CH:28]=[CH:27][C:24]([O:25][CH3:26])=[CH:23][CH:22]=2)=[O:19])[CH:17]=[CH:16][C:13]([O:14][CH3:15])=[CH:12][CH:11]=1>CCOCC>[CH3:9][O:8][C:5]1[CH:6]=[CH:7][C:2]([C:18]([C:10]2[CH:11]=[CH:12][C:13]([O:14][CH3:15])=[CH:16][CH:17]=2)([OH:19])[CH2:20][C:21]2[CH:22]=[CH:23][C:24]([O:25][CH3:26])=[CH:27][CH:28]=2)=[CH:3][CH:4]=1

Participants

4

Reactant 2

HCID 77304-BromoanisoleHCID 67120Desoxyanisoin

Product 1

HCID 198342771,1,2-Tris(4-methoxyphenyl)ethan-1-ol

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

To the Grignard reagent prepared from 20 g 4-bromoanisole (107 mmol) and 2.43 g Mg turnings (107 mg-atom) in 20 mL Et2O was added 19.25 g dry (P2O5) desoxyanisoin (76 mmol) as a solid in four portions, each followed by a 50 mL wash of Et2O. The mixture was stirred at reflux 17 h, cooled to room temperature, poured onto 200 g ice and 40 mL 1N H2SO4, and filtered into a separatory funnel. 100 mL Et2O was added and the organic layer was washed with 100 mL H2O and saturated NaHCO3 (2×100 mL). The organic layer was dried (MgSO4), filtered, and the Et2O was removed under reduced pressure to give crude 1,1,2-Tris(4-methoxyphenyl)ethanol as an orange oil which crystallized (25 mL EtOH with a trace of NH4OH) as an orange solid, 18.6 g (67% crude yield), mp: 109°-127° C.; NMR δ7.47 to 6.63 (m, 12H, ArH), 3.73 (3 overlapping s, 9H, OCH3), 3.48 (s, 2H, CH2), 2.27 (s, 1H, OH). p-TsOH.H2O (2 g; 10.5 mmol) and 18.5 g of the crude carbinol (50.8 mmol) were dissolved in 50 mL C6H6, heated to reflux 2 h, cooled to room temperature, and poured onto 75 mL 5% NaHCO3. The organic layer was washed with 75 mL 5% NaHCO3. The combined aqueous layers were extracted with 25 mL C6H6. The combined organic layers were washed with 100 mL H2O, dried (Na2SO4), filtered, and the solvent removed to give a dark oil. The oil was purified on 80 g flash SiO2 (gradient elution with petroleum ether-CH2Cl 2) yielding an amber oil which solidified at room temperature to yield 1,1,2-Tris(4-methoxyphenyl)ethene as white cubes (11.3 g, 64%), mp: 100°-101° C. (lit. 100°-101° C.). NMR δ7.29 to 6.55 (m, 13H, ArH and C=CH), 3.78 (s, 3H, geminal ring OCH3), 3.75 (s, 3H, vicinal ring OCH3), 3.69 (s, 3H, central ring OCH3).

Workup

  1. additionwas added 19.25 g
  2. washwash of Et2O
  3. temperatureat reflux 17 h
  4. additionpoured onto 200 g ice and 40 mL 1N H2SO4
  5. filtrationfiltered into a separatory funnel
  6. addition100 mL Et2O was added
  7. washthe organic layer was washed with 100 mL H2O and saturated NaHCO3 (2×100 mL)
  8. dry with materialThe organic layer was dried (MgSO4)
  9. filtrationfiltered
  10. customthe Et2O was removed under reduced pressure

Sources & evidence

ORD record
ord-975c6341b390424c834a0b4661ec4e80
Source dataset
uspto-grants-1991_05
Patent number
US05015666

Reaction notes

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