Water → 2-(1H-Pyrrol-1-Yl)Phenol

HRID 1907976Notes

Reaction equation

HRID 1907976 reaction equation
O.[NH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[OH:9].CO[CH:12]1[CH2:16][CH2:15][CH:14](OC)O1>C(O)(=O)C>[N:2]1([C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[OH:9])[CH:12]=[CH:16][CH:15]=[CH:14]1

Participants

5

Reactant 3

HCID 962WaterHCID 58012-AminophenolHCID 790982,5-Dimethoxytetrahydrofuran

Product 1

HCID 7123342-(1H-Pyrrol-1-Yl)PhenolYield 74.1%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
100 °C

Procedure

A 5 L 3-neck round bottom flask was fitted with a mechanical stirrer, a heating mantle, a water cooled reflux condenser, a temperature probe/controller and a nitrogen inlet/outlet. The vessel was charged with (50 g, 0.46 mol) of 2-aminophenol and acetic acid (750 mL) which provided a very dark solution. Stirring was commenced and the vessel was charged with 2,5-dimethoxytetrahydrofuran (59.4 mL, 0.458 mol) dropwise over 2 minutes. The dark mixture was then heated at 100° C. for 15 min. The mixture was allowed to cool to room temperature and was filtered through a pad of Celite to remove residual solids. The filtrate was concentrated under reduced pressure azeotroping with toluene. The residual oil was dissolved in ethyl acetate (1000 mL) and was partitioned with water (500 mL). The organic layer was separated and was washed with water (500 mL), dried over sodium sulfate and filtered. The filtrate was concentrated under reduced pressure to provide 2-(1H-pyrrol-1-yl)phenol (54 g, 74%) as a dark oil. ESI-MS m/z calc. 159.1. found 160.2 (M+1)+. Retention time: 2.67 minutes (3 min run). 1H NMR (400 MHz, CDCl3) δ 7.37-7.23 (m, 2H), 7.13-6.97 (m, 2H), 6.91 (t, J=1.9 Hz, 2H), 6.43 (t, J=1.9 Hz, 2H), 5.35 (s, 1H). 3-(1H-Pyrrol-1-yl)pyridin-2-ol was also synthesized using the procedure described above.

Workup

  1. customA 5 L 3-neck round bottom flask was fitted with a mechanical stirrer
  2. temperaturereflux condenser
  3. customprovided a very dark solution
  4. temperatureto cool to room temperature
  5. filtrationwas filtered through a pad of Celite
  6. customto remove residual solids
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. customazeotroping with toluene
  9. dissolutionThe residual oil was dissolved in ethyl acetate (1000 mL)
  10. customwas partitioned with water (500 mL)
  11. customThe organic layer was separated
  12. washwas washed with water (500 mL)
  13. dry with materialdried over sodium sulfate
  14. filtrationfiltered
  15. concentrationThe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-d42e2d0af18c4d0282ce10186c796bbd
Source dataset
uspto-grants-2013_12
Patent number
US08598164B2

Reaction notes

Loading…