Hydrochloric Acid → 2-Hydroxy-5-phenoxybenzaldehyde

HRID 2214873Notes

Reaction equation

HRID 2214873 reaction equation
C([Mg]Br)C.[O:5]([C:12]1[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.CN(P(N(C)C)(N(C)C)=O)C.[CH2:30]=[O:31].Cl>C(OCC)C.C1(C)C=CC=CC=1>[O:5]([C:12]1[CH:13]=[C:14]([CH:30]=[O:31])[C:15]([OH:18])=[CH:16][CH:17]=1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 12679HexamethylphosphoramideHCID 132544-PhenoxyphenolHCID 178418443HCID 178418443, compound

Product 1

HCID 149712582-Hydroxy-5-phenoxybenzaldehydeYield 42%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
80 °C

Procedure

Ethyl magnesium bromide (67.5 mL of an approximately 3.0 M solution in diethyl ether, 202.5 mmol) was added to toluene (50 mL). A solution of 4-phenoxyphenol (25.00 g, 134.26 mmol) in diethyl ether (35 mL) was added resulting in the evolution of gas. The reaction was heated to 80° C. causing distillation of the diethyl ether. Toluene (300 mL), HMPA (23.4 mL, 24.059 g, 134.26 mmol), and paraformaldehyde (10.07 g, 335.65 mmol) were added and the reaction was heated to 85° C. for 4 hours. The reaction was cooled to room temperature and was acidified with 2N HCl. The resulting layers were separated and the organic phase collected. The organic phase was washed with brine. The combined aqueous phases were extracted with methylene chloride. The organic phases were combined, dried over MgSO4, filtered and concentrated in vacuo yielding a yellow oil. The oil was purified by silica flash chromatography (hexanes-ethyl acetate, 95:5). Concentration in vacuo of the desired fractions provided the salicylaldehyde as a pale yellow powder (12.0 g, 42%) of suitable purity to use in subsequent steps.

Workup

  1. customresulting in the evolution of gas
  2. distillationdistillation of the diethyl ether
  3. temperaturethe reaction was heated to 85° C. for 4 hours
  4. temperatureThe reaction was cooled to room temperature
  5. customThe resulting layers were separated
  6. customthe organic phase collected
  7. washThe organic phase was washed with brine
  8. extractionThe combined aqueous phases were extracted with methylene chloride
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customyielding a yellow oil
  13. customThe oil was purified by silica flash chromatography (hexanes-ethyl acetate, 95:5)
  14. concentrationConcentration in vacuo of the desired fractions

Sources & evidence

ORD record
ord-666a9b2a1a9f4705a745783f62c6d6ae
Source dataset
uspto-grants-2006_09
Patent number
US07109211B2

Reaction notes

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